RESUMEN
Despite the decrease in mortality and morbidity due to SARS-CoV-2 infection, the incidence of infections due to Omicron subvariants of SARS-CoV-2 remains high. The mutations acquired by these subvariants, mainly concentrated in the receptor-binding domain (RBD), have caused a shift in infectivity and transmissibility, leading to a loss of effectiveness of the first authorized COVID-19 vaccines, among other reasons, by neutralizing antibody evasion. Hence, the generation of new vaccine candidates adapted to Omicron subvariants is of special interest in an effort to overcome this immune evasion. Here, an optimized COVID-19 vaccine candidate, termed MVA-S(3P_BA.1), was developed using a modified vaccinia virus Ankara (MVA) vector expressing a full-length prefusion-stabilized SARS-CoV-2 spike (S) protein from the Omicron BA.1 variant. The immunogenicity and efficacy induced by MVA-S(3P_BA.1) were evaluated in mice in a head-to-head comparison with the previously generated vaccine candidates MVA-S(3P) and MVA-S(3Pbeta), which express prefusion-stabilized S proteins from Wuhan strain and Beta variant, respectively, and with a bivalent vaccine candidate composed of a combination of MVA-S(3P) and MVA-S(3P_BA.1). The results showed that all four vaccine candidates elicited, after a single intramuscular dose, protection of transgenic K18-hACE2 mice challenged with SARS-CoV-2 Omicron BA.1, reducing viral loads, histopathological lesions, and levels of proinflammatory cytokines in the lungs. They also elicited anti-S IgG and neutralizing antibodies against various Omicron subvariants, with MVA-S(3P_BA.1) and the bivalent vaccine candidate inducing higher titers. Additionally, an intranasal immunization in C57BL/6 mice with all four vaccine candidates induced systemic and mucosal S-specific CD4+ and CD8+ T-cell and humoral immune responses, and the bivalent vaccine candidate induced broader immune responses, eliciting antibodies against the ancestral Wuhan strain and different Omicron subvariants. These results highlight the use of MVA as a potent and adaptable vaccine vector against new emerging SARS-CoV-2 variants, as well as the promising feature of combining multivalent MVA vaccine candidates.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , Ratones Transgénicos , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Animales , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Ratones , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Humanos , Enzima Convertidora de Angiotensina 2/inmunología , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Femenino , Vacunas de ADN/inmunología , Virus Vaccinia/inmunología , Virus Vaccinia/genética , Inmunogenicidad VacunalRESUMEN
Background: DS-5670 is a messenger ribonucleic acid (mRNA) vaccine platform targeting the receptor-binding domain (RBD) of the spike protein derived from severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Booster vaccination against coronavirus disease 2019 (COVID-19) with monovalent DS-5670a (incorporating mRNA encoding the RBD from the original SARS-CoV-2 strain) or bivalent DS-5670a/b (original and omicron BA.4-5 RBD antigens) is effective and safe in adults. Data from a phase 2/3 active-controlled, non-inferiority, pediatric study evaluating a third booster dose of DS-5670a/b are reported here. Methods: Children aged 5-11 years who had completed the two-dose primary vaccination series with monovalent BNT162b2 (original strain) at least 3 months prior to enrolment were randomly assigned to receive DS-5670a/b (20 µg of mRNA) or bivalent BNT1 62b2 (original/omicron BA.4-5; 10 µg of mRNA) on Day 1. The primary efficacy endpoint was blood neutralization geometric mean titer (GMT) against SARS-CoV-2 (omicron variant BA.5.2.1) and immune response rate (≥ 4-fold increase in post-vaccination circulating anti-SARS-CoV-2 neutralizing activity) on Day 29. Results: Among evaluable participants (DS-5670a/b, n = 74; bivalent BNT162b2, n = 75), the adjusted GMT ratio of DS-5670a/b to bivalent BNT162b2 on Day 29 was 1.636 (95% CI, 1.221, 2.190). Immune response rates were ≥ 89% with both study vaccines; adjusted difference 2.6% (95% CI, -7.8, 13.8). The prespecified non-inferiority margins were exceeded, and the study met the primary endpoint. DS-5670a/b also demonstrated broad neutralization activity across recent omicron sublineages and no cases of COVID-19 between Days 8-29 post-administration were reported. There were no novel safety concerns in the pediatric population at data cut-off. Conclusions: Bivalent DS-5670a/b was non-inferior to bivalent BNT162b2 in terms of immunogenicity, and had a manageable safety profile, when administered as a heterologous booster in children aged 5-11 years. Clinical trial registration: https://jrct.niph.go.jp/, identifier jRCT2031220665.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , SARS-CoV-2/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Femenino , Preescolar , Niño , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Glicoproteína de la Espiga del Coronavirus/inmunología , Inmunogenicidad Vacunal , Vacuna BNT162/inmunología , Vacunación/métodosRESUMEN
Introduction: Various COVID-19 vaccine trials have shown that vaccines can successfully prevent symptomatic cases of COVID-19 and death. Head-to-head comparisons help to better understand the immune response characteristics of different COVID-19 vaccines in humans. Methods: We randomly selected 20 participants from each of five ongoing Phase II trials of COVID-19 vaccines. Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months. RBD-IgG titres were detected by ELISA, neutralising antibody titer were detected by pseudoviral neutralization and immune cell response were detected by flow cytometry. Results: At the first visit (V1), 100% of individuals who received the BNT162b2, CONVIDECIA, or KCONVAC vaccines experienced seroconversion of neutralizing and binding antibodies in the serum. Except for the Recombinant COVID-19 Vaccine (Sf9 Cells) vaccine having the highest neutralizing antibody GMT at the second visit (although there was no statistically significant difference in geometric mean titers between V1 and V2), the rest of the vaccines had the highest levels of binding antibodies and neutralizing antibodies at V1. The neutralizing antibodies GMT of all vaccines showed a significant decrease at V3 compared to V1. The neutralizing antibody GMT against the omicron variant of all vaccines at V1 showed a significant decrease compared to the wild strain. We observed statistically significant differences in Tcm cells and RBD-specific memory B cells among various vaccines. Discussion: BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine).
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunidad Celular , Inmunidad Humoral , SARS-CoV-2 , Humanos , Vacunas contra la COVID-19/inmunología , Adulto , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Masculino , Femenino , China , Persona de Mediana Edad , Adulto Joven , Vacunas de Subunidad/inmunología , Vacunas de ADN/inmunología , Vacuna BNT162/inmunología , Inmunogenicidad Vacunal , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Background: Concomitant administration of COVID-19, influenza, and pneumococcal vaccines could reduce the burden on healthcare systems. However, the immunogenicity and safety of various combinations of a third booster dose of SARS-CoV-2 inactivated vaccine (CoronaVac), inactivated quadrivalent influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23), particularly in different age groups, is still unknown. Methods: A phase 4, randomized, open-label, controlled trial was conducted in Beijing, China. 636 healthy adults were divided into two age groups (18-59 and ≥60 years) and randomized equally into three groups: CoronaVac and IIV4 followed by PPV23; CoronaVac and PPV23 followed by IIV4; or CoronaVac followed by IIV4 and PPV23, with a 28-day interval between vaccinations. Immunogenicity was evaluated by measuring antibody titers, and safety was monitored. ClinicalTrials.gov Identifier: NCT05298800. Results: Co-administration of a third dose of CoronaVac, IIV4, and PPV23 in any combination was safe. Among adults aged 18-59, co-administration with PPV23 maintained non-inferiority of antibody levels for CoronaVac and IIV4, despite a slight reduction in antibody responses. This reduction was not observed in participants ≥60 years. Furthermore, co-administration of IIV4 and PPV23 affected seroconversion rates for both vaccines. Conclusions: Co-administration of the third dose of SARS-CoV-2 inactivated vaccine with the influenza vaccine, followed by PPV23, may be optimal for adults aged 18-59. In adults ≥60, all vaccine combinations were immunogenic, suggesting a flexible vaccination approach. Since antibody measurements were taken 28 days post-vaccination, ongoing surveillance is essential to assess the longevity of the immune responses.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , Vacunas contra la Influenza , Vacunas Neumococicas , SARS-CoV-2 , Humanos , Persona de Mediana Edad , Vacunas Neumococicas/inmunología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/efectos adversos , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Adulto , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/administración & dosificación , Anciano , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Adulto Joven , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/efectos adversos , Adolescente , China , Gripe Humana/prevención & control , Gripe Humana/inmunologíaRESUMEN
Lung transplant recipients (LTRs) are particularly at risk of developing severe coronavirus disease-2019 (COVID-19), but are also difficult to protect by vaccination due to their immunocompromised state. Here, we investigated the immunogenicity of mRNA-based COVID-19 vaccines in LTRs who had a prior natural SARS-CoV-2 infection. At a median of 184 days after SARS-CoV-2 infection, LTRs were vaccinated twice with the mRNA-1273 COVID-19 vaccine, with a 28-day interval. Blood samples were obtained pre-vaccination, 28 days after the first dose, and 28 days and 6 months after the second dose. Spike (S-) and nucleocapsid (N-) specific antibodies were measured, as well as neutralization of the ancestral and Omicron BA.5 variant. S-specific T cell responses were evaluated using IFN-γ ELISpotï¼IGRA, and activation markers by flow cytometry. Phenotyping of T cells was performed by using high-resolution spectral flow cytometry. Most LTRs with prior infection had detectable S-specific antibodies and T cells at baseline. After the first vaccination, S-specific antibody levels increased significantly; an additional increase was observed after the second vaccination. N-specific antibodies decreased during the study period, indicative of the fact that no further breakthrough infections occurred. An increase in IFN-γ producing T cells was observed after the first vaccination, but no additional boost could be detected after the second vaccination. Antibody levels and virus-specific T cell responses remained significantly higher compared to pre-vaccination levels at 6 months post-vaccination, indicating an additive and durable effect of vaccination after infection in LTRs. Neutralizing antibodies were detected against the ancestral strain and retained cross-reactivity with Omicron BA.5, albeit at lower levels. Moreover, the quantity and phenotype of SARS-CoV-2 spike-specific T cells were similar in LTRs compared to controls with hybrid immunity. In conclusion, mRNA-based COVID-19 vaccines are immunogenic in LTRs with prior immunity, and antibody and T cell responses are durable up to 6 months post-vaccination.
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Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Trasplante de Pulmón , SARS-CoV-2 , Linfocitos T , Receptores de Trasplantes , Humanos , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Linfocitos T/inmunología , SARS-CoV-2/inmunología , Persona de Mediana Edad , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacuna nCoV-2019 mRNA-1273/inmunología , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Glicoproteína de la Espiga del Coronavirus/inmunología , Anciano , Vacunación , Inmunogenicidad VacunalRESUMEN
This phase 1 trial assessed the safety and immunogenicity of an investigational tetanus/diphtheria/acellular pertussis vaccine combined with CpG 1018 adjuvant 1500 µg (Tdap-1018 1500 µg) or 3000 µg (Tdap-1018 3000 µg) in adults and adolescents. In this randomized, active-controlled, multicenter, dose-escalation trial, healthy participants aged 10 to 22 years received 1 dose of Tdap-1018 1500 µg, Tdap-1018 3000 µg, or Boostrix. Geometric mean concentrations (GMCs) and booster response rates (BRRs) for antibodies against pertussis (pertussis toxin, filamentous hemagglutinin, pertactin), tetanus, and diphtheria antigens, and neutralizing antibodies against pertussis toxin were assessed 4 weeks after vaccination. Safety and tolerability were assessed for solicited post-injection reactions within 7 days after vaccination and unsolicited adverse events up to 12 weeks after vaccination. Of 117 enrolled participants, 80 adults (92%) and 30 adolescents (100%) completed the study. Both Tdap-1018 formulations were generally well tolerated, with no vaccine-related serious adverse events. Frequency and severity in post-injection reactions after Tdap-1018 administration were similar to Boostrix except for higher proportions of moderate pain for Tdap-1018. In adults at week 4, ratio of GMCs and BRRs for all antigens in the 3000-µg group were similar to or higher than Boostrix, with significantly higher GMC ratios for anti-pertussis toxin (2.1 [1.5-3.0]) and anti-tetanus (1.8 [1.1-2.9]) and significantly higher BRRs for anti-pertussis toxin (difference [95% CI]: 34.5% [13.4-54.6]), anti-pertactin (19.2% [4.4-38.1]), and anti-tetanus (30.0% [3.6-52.7]) antibodies. For adolescents, in the 3000-µg group, ratio of GMCs and BRRs were similar to or higher than Boostrix for all antigens. Both Tdap-1018 formulations showed acceptable safety and tolerability profiles. Tdap-1018 3000 µg induced similar or higher immune responses than Boostrix. ACTRN12620001177943 (Australian New Zealand Clinical Trials Registry; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=ACTRN12620001177943p).
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Adyuvantes Inmunológicos , Anticuerpos Antibacterianos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular , Inmunización Secundaria , Oligodesoxirribonucleótidos , Tos Ferina , Humanos , Adolescente , Femenino , Masculino , Anticuerpos Antibacterianos/sangre , Inmunización Secundaria/métodos , Adulto , Adulto Joven , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/efectos adversos , Niño , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Tos Ferina/prevención & control , Tos Ferina/inmunología , Anticuerpos Neutralizantes/sangre , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Tétanos/prevención & control , Tétanos/inmunología , Voluntarios Sanos , Inmunogenicidad VacunalRESUMEN
INTRODUCTION: Vaccination against SARS-CoV-2 is an integral pillar of the public health approach to COVID-19. With the emergence of variants of concern that increase transmissibility and escape from vaccine- or infection-induced protection, vaccines have been developed to more closely match the newly circulating SARS-CoV-2 strains to improve protection. The safety and immunogenicity of multiple authorized messenger RNA (mRNA)-based COVID-19 vaccines targeting the omicron sublineage (BA.1, BA.4/BA.5, and XBB.1.5) have been demonstrated in several clinical trials among adults and children. AREAS COVERED: This review will comprehensively detail the available evidence (published through July 2024) from ongoing clinical trials on omicron variant-containing mRNA-1273 vaccines administered as additional doses in previously vaccinated target demographics. EXPERT OPINION: Across three clinical trials, omicron variant-containing mRNA-1273 vaccines induced immune responses to vaccine-matched omicron strains as well as ancestral SARS-CoV-2, with a safety and reactogenicity profile comparable to the original mRNA-1273 vaccine. Combined with pivotal data demonstrating the safety, efficacy, and effectiveness of the original mRNA-1273 vaccine, these findings support the use of variant-containing mRNA-1273 vaccines and provide confidence that expeditious development of updated vaccines using this established mRNA platform can maintain protection against COVID-19.
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Vacuna nCoV-2019 mRNA-1273 , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , SARS-CoV-2 , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/efectos adversos , Vacuna nCoV-2019 mRNA-1273/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Inmunización Secundaria/métodos , Adulto , NiñoRESUMEN
In this study, we conducted a case-control investigation to assess the immunogenicity and effectiveness of primary and first booster homologous and heterologous COVID-19 vaccination regimens against infection and hospitalization, targeting variants circulating in Lebanon during 2021-2022. The study population comprised active Lebanese military personnel between February 2021 and September 2022. Vaccine effectiveness (VE) against laboratory-confirmed SARS-CoV-2 infection and associated hospitalization was retrospectively determined during different variant-predominant periods using a case-control study design. Vaccines developed by Sinopharm, Pfizer, and AstraZeneca as well as Sputnik V were analyzed. Prospective assessment of humoral immune response, which was measured based on the SARS-CoV-2 antispike receptor binding domain IgG titer, was performed post vaccination at various time points, focusing on Sinopharm and Pfizer vaccines. Statistical analyses were performed using IBM SPSS and GraphPad Prism. COVID-19 VE remained consistently high before the emergence of the Omicron variant, with lower estimates during the Delta wave than those during the Alpha wave for primary vaccination schemes. However, vaccines continued to offer significant protection against infection. VE estimates consistently decreased for the Omicron variant across post-vaccination timeframes and schemes. VE against hospitalization declined over time and was influenced by the variant. No breakthrough infections progressed to critical or fatal COVID-19. Immunogenicity analysis revealed that the homologous Pfizer regimen elicited a stronger humoral response than Sinopharm, while a heterologous Sinopharm/Pfizer regimen yielded comparable results to the Pfizer regimen. Over time, both Sinopharm's and Pfizer's primary vaccination schemes exhibited decreased humoral immunity titers, with Pfizer being a more effective booster than Sinopharm. This study, focusing on healthy young adults, provides insights into VE during different pandemic waves. Continuous research and monitoring are essential for understanding vaccine-mediated immune responses under evolving circumstances.
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Vacunas contra la COVID-19 , COVID-19 , Hospitalización , Inmunización Secundaria , SARS-CoV-2 , Humanos , Líbano/epidemiología , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Masculino , Hospitalización/estadística & datos numéricos , Adulto , Femenino , Estudios de Casos y Controles , Eficacia de las Vacunas , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Inmunogenicidad Vacunal , Personal Militar , Adulto Joven , Estudios Retrospectivos , Vacunación , Inmunidad HumoralRESUMEN
BACKGROUND: BBV152 (Covaxin™) is a whole-virion inactivated SARS-CoV-2 vaccine mixed with an immune adjuvant. We aimed to compare immune responses after booster vaccination with heterologous BBV152 versus homologous mRNA vaccine. METHODS: We conducted a randomized, participant-blinded, controlled trial. Fifty mRNA-vaccinated participants were enrolled and randomized to receive an mRNA booster (n = 26) or BBV152 (n = 24). Blood samples were collected pre-vaccination, and at Day 7, 28, 180 and 360 post-booster for analysis of humoral and cellular immune responses. Primary end point was the SARS-CoV-2 anti-spike antibody titer at day 28. RESULTS: Recruitment began in January 2022 and was terminated early due to the BBV152 group meeting pre-specified criteria for futility. At Day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBV152 (2004 IU/mL; 95 % confidence interval [CI], 1132-3548) vs mRNA (26,669 IU/mL; 95 % CI, 21,330-33,266; p < 0.0001), but comparable levels of spike-specific CD4 and cytotoxic T-cells were observed. Anti-spike antibody titers remained significantly different at Day 180: BBV152 4467 IU/mL (95 % CI, 1959-10,186) vs mRNA 20,749 IU/mL (95 % CI, 12,303-35,075; p = 0.0017). Levels of surrogate virus neutralizing antibodies against ancestral and Omicron subvariants BA.1 and BA.2 were significantly higher among mRNA recipients at Day 180, including after adjusting for intercurrent infection. By Day 360, anti-spike antibody titers and neutralizing antibody levels against Omicron subvariants became similar between vaccine groups. By the end of the study, 16 in each arm (mRNA 64 % and BBV152 69.6 %) had breakthrough infections and time to COVID-19 infection between vaccine groups were similar (p = 0.63). CONCLUSIONS: Wild-type SARS-CoV-2 anti-spike antibody titer and surrogate virus neutralizing test levels against wild-type SARS-CoV-2 and Omicron subvariants BA.1/BA.2/BA.5 were significantly higher at Day 28 and 180 in individuals who received booster vaccination with an mRNA vaccine compared with BBV152. CLINICAL TRIAL REGISTRATION NUMBER: NCT05142319.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Femenino , Masculino , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Adulto , Inmunización Secundaria/métodos , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de ARNm/inmunología , Adulto Joven , Inmunidad Humoral , Inmunidad Celular , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificaciónRESUMEN
Background: Transmission-blocking vaccines (TBVs) can effectively prevent the community's spread of malaria by targeting the antigens of mosquito sexual stage parasites. At present, only a few candidate antigens have demonstrated transmission-blocking activity (TBA) potential in P. vivax. Quiescin-sulfhydryl oxidase (QSOX) is a sexual stage protein in the rodent malaria parasite Plasmodium berghei and is associated with a critical role in protein folding by introducing disulfides into unfolded reduced proteins. Here, we reported the immunogenicity and transmission-blocking potency of the PvQSOX in P. vivax. Methods and findings: The full-length recombinant PvQSOX protein (rPvQSOX) was expressed in the Escherichia coli expression system. The anti-rPvQSOX antibodies were generated following immunization with the rPvQSOX in rabbits. A parasite integration of the pvqsox gene into the P. berghei pbqsox gene knockout genome was developed to express full-length PvQSOX protein in P. berghei (Pv-Tr-PbQSOX). In western blot, the anti-rPvQSOX antibodies recognized the native PvQSOX protein expressed in transgenic P. berghei gametocyte and ookinete. In indirect immunofluorescence assays, the fluorescence signal was detected in the sexual stages, including gametocyte, gamete, zygote, and ookinete. Anti-rPvQSOX IgGs obviously inhibited the ookinetes and oocysts development both in vivo and in vitro using transgenic parasites. Direct membrane feeding assays of anti-rPvQSOX antibodies were conducted using four field P. vivax isolates (named isolates #1-4) in Thailand. Oocyst density in mosquitoes was significantly reduced by 32.00, 85.96, 43.52, and 66.03% with rabbit anti-rPvQSOX antibodies, respectively. The anti-rPvQSOX antibodies also showed a modest reduction of infection prevalence by 15, 15, 20, and 22.22%, respectively, as compared to the control, while the effect was insignificant. The variation in the DMFA results may be unrelated to the genetic polymorphisms. Compared to the P.vivax Salvador (Sal) I strain sequences, the pvqsox in isolate #1 showed no amino acid substitution, whereas isolates #2, #3, and #4 all had the M361I substitution. Conclusions: Our results suggest that PvQSOX could serve as a potential P. vivax TBVs candidate, which warrants further evaluation and optimization.
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Anticuerpos Antiprotozoarios , Vacunas contra la Malaria , Malaria Vivax , Plasmodium berghei , Plasmodium vivax , Proteínas Recombinantes , Plasmodium vivax/inmunología , Plasmodium vivax/genética , Plasmodium vivax/enzimología , Animales , Conejos , Vacunas contra la Malaria/inmunología , Anticuerpos Antiprotozoarios/inmunología , Malaria Vivax/prevención & control , Malaria Vivax/transmisión , Malaria Vivax/inmunología , Plasmodium berghei/inmunología , Plasmodium berghei/genética , Plasmodium berghei/enzimología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Ratones , Escherichia coli/genética , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Proteínas Protozoarias/inmunología , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Femenino , Humanos , Inmunogenicidad Vacunal , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: In response to the coronavirus disease 2019 (Covid-19) pandemic, Brazil authorised the Astra Zeneca/Fiocruz vaccine in January 2021. As the Delta variant emerged in May 2021, interval between vaccine doses was adjusted. By September 2021, the Brazilian National Immunisation Program recommended a booster dose for individuals over 70, and later expanded the recommendation to all adults. OBJECTIVES: Assess the equivalence of IgG antibody response against the Covid-19 S protein before and approximately 28 days after the third dose of a Covid-19 recombinant vaccine. Two groups received initial two doses with intervals of eight and 12 weeks. METHODS: This is a phase IV clinical study, uncontrolled, non-randomised. The study proposes calculating the ratio of geometric means titres (GMT) 28 days after the third dose, with a target ratio of confidence interval (CI) between 0.77 and 1.3. FINDINGS: In the primary endpoint, there was no equivalence between the eight- and 12-week intervals with a slight variation favouring the eight-week group. Post-third dose, both groups showed increases titres at 28 days, three months, six months and 12 months. Both groups responded similarly to Delta and Omicron BA.1, with a more significant increase for Delta. MAIN CONCLUSIONS: The study showed strong and consistent immune response in all age groups receiving the Covid-19 recombinant vaccine. Third dose elicited an increase in GMT by at least three times aligned with Ministry of Health strategies emphasising Bio-Manguinhos crucial role in pandemic control in the country.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Esquemas de Inmunización , Inmunización Secundaria , Inmunogenicidad Vacunal , Inmunoglobulina G , SARS-CoV-2 , Vacunas Sintéticas , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Masculino , Adulto , Femenino , Persona de Mediana Edad , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Inmunoglobulina G/sangre , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Adulto Joven , Anciano , Brasil , Adolescente , Factores de TiempoRESUMEN
BACKGROUND: Pregnancy is a critical time for women, making them more susceptible to infectious diseases like COVID-19. This study aims to determine the immunogenicity of COVID-19 in pregnant women who have been infected compared to those who have received the inactive COVID-19 vaccine. MATERIALS AND METHODS: In this retrospective cohort study, pregnant women who received the inactivated COVID-19 vaccine (Sinopharm) and those with a history of COVID-19 infection during pregnancy were studied. Participants who had experienced stillbirth, received different COVID-19 vaccines, or had intrauterine fetal death were excluded from the study. Overall, the study included 140 participants. The participants were divided into two groups of 70 participants - pregnant women who received the Sinopharm vaccine and pregnant women who had COVID-19 infection during pregnancy. Before delivery, blood samples were collected from all mothers to evaluate the maternal immunoglobulin G (IgG) level. Blood samples were also taken from the baby's umbilical cord during delivery to measure the newborn's IgG level. Additionally, blood samples were collected from babies whose mothers showed signs of acute infection to measure their IgM levels and evaluate vertical transmission. FINDINGS: The study found a significant relationship between the mean level of maternal IgG and umbilical cord IgG within the groups (P < 0.001). The highest levels of maternal IgG (2.50 ± 2.17) and umbilical cord IgG (2.43 ± 2.09) were observed in pregnant women with a previous COVID-19 infection and no history of vaccination (P < 0.001). Only one baby was born with a positive IgM, and this baby was born to a mother who showed signs of COVID-19 infection in the last five days of pregnancy. The mother was 28 years old, with a BMI of 33; it was her first pregnancy, and she gave birth to a male newborn at term. CONCLUSION: Administering an inactivated vaccine during pregnancy can generate immunity in both the mother and the child. However, the vaccine's immunity level may not be as potent as that conferred by COVID-19 infection during pregnancy. Nonetheless, the risk of vertical transmission of COVID-19 is considered minimal and can be classified as negligible.
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Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunoglobulina G , Complicaciones Infecciosas del Embarazo , SARS-CoV-2 , Humanos , Embarazo , Femenino , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios Retrospectivos , Inmunoglobulina G/sangre , Adulto , Complicaciones Infecciosas del Embarazo/prevención & control , Complicaciones Infecciosas del Embarazo/inmunología , SARS-CoV-2/inmunología , Anticuerpos Antivirales/sangre , Vacunación , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Recién Nacido , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Mujeres Embarazadas , Inmunogenicidad VacunalRESUMEN
Vaccine safety and immunogenicity data in human immunodeficiency virus (HIV)-exposed uninfected (HEU) children are important for decision-making in HIV and typhoid co-endemic countries. In an open-label study, we recruited Malawian HEU and HIV unexposed uninfected (HUU) infants aged 9 - 11 months. HEU participants were randomized to receive Vi-tetanus toxoid conjugate vaccine (Vi-TT) at 9 months, Vi-TT at 15 months, or Vi-TT at 9 and 15 months. HUU participants received Vi-TT at 9 and 15 months. Safety outcomes included solicited and unsolicited adverse events (AE) and serious AEs (SAEs) within 7 days, 28 days, and 6 months of vaccination, respectively. Serum was collected before and at day 28 after each vaccination to measure anti-Vi IgG antibodies by enzyme-linked immunosorbent assay (ELISA). Cohort 1 (66 participants) enrollment began 02 December 2019, and follow-up was terminated before completion due to the COVID-19 pandemic. Cohort 2 (100 participants) enrollment began 25 March 2020. Solicited AEs were mostly mild, with no significant differences between HEU and HUU participants or one- and two-dose groups. All six SAEs were unrelated to vaccination. Anti-Vi geometric mean titers (GMT) increased significantly from 4.1 to 4.6 ELISA units (EU)/mL at baseline to 2572.0 - 4117.6 EU/mL on day 28 post-vaccination, and similarly between HEU and HUU participants for both one- and two-dose schedules. All participants seroconverted (>4-fold increase in GMT) by the final study visit. Our findings of comparable safety and immunogenicity of Vi-TT in HUU and HEU children support country introductions with single-dose Vi-TT in HIV-endemic countries.
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Anticuerpos Antibacterianos , Infecciones por VIH , Inmunogenicidad Vacunal , Fiebre Tifoidea , Vacunas Tifoides-Paratifoides , Vacunas Conjugadas , Humanos , Masculino , Femenino , Malaui , Lactante , Infecciones por VIH/inmunología , Vacunas Tifoides-Paratifoides/inmunología , Vacunas Tifoides-Paratifoides/efectos adversos , Vacunas Tifoides-Paratifoides/administración & dosificación , Vacunas Conjugadas/inmunología , Vacunas Conjugadas/efectos adversos , Vacunas Conjugadas/administración & dosificación , Anticuerpos Antibacterianos/sangre , Fiebre Tifoidea/inmunología , Fiebre Tifoidea/prevención & control , Inmunoglobulina G/sangre , Toxoide Tetánico/inmunología , Toxoide Tetánico/efectos adversos , Toxoide Tetánico/administración & dosificación , Esquemas de Inmunización , VacunaciónRESUMEN
Background: Antibody-mediated protection can depend on mechanisms varying from neutralization to Fc-dependent innate immune-cell recruitment. Adjuvanted vaccine development relies on a holistic understanding of how adjuvants modulate the quantity/titer and quality of the antibody response. Methods: A Phase 2 trial (ClinicalTrials.gov: NCT00805389) evaluated hepatitis B vaccines formulated with licensed adjuvants (AS01B, AS01E, AS03, AS04 or Alum) in antigen-naïve adults. The trial investigated the role of adjuvants in shaping antibody-effector functions, and identified an innate transcriptional response shared by AS01B, AS01E and AS03. We integrated previously reported data on the innate response (gene expression, cytokine/C-reactive protein levels) and on quantitative/qualitative features of the mature antibody response (Fc-related parameters, immunoglobulin titers, avidity). Associations between the innate and humoral parameters were explored using systems vaccinology and a machine-learning framework. Results: A dichotomy in responses between AS01/AS03 and AS04/Alum (with the former two contributing most to the association with the humoral response) was observed across all timepoints of this longitudinal study. The consistent patterns over time suggested a similarity in the impacts of the two-dose immunization regimen, year-long interval, and non-adjuvanted antigenic challenge given one year later. An innate signature characterized by interferon pathway-related gene expression and secreted interferon-γ-induced protein 10 and C-reactive protein, which was shared by AS01 and AS03, consistently predicted both the qualitative antibody response features and the titers. The signature also predicted from the antibody response quality, the group of adjuvants from which the administered vaccine was derived. Conclusion: An innate signature induced by AS01- or AS03-adjuvanted vaccines predicts the antibody response magnitude and quality consistently over time.
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Vacunas contra Hepatitis B , Inmunidad Innata , Humanos , Inmunidad Innata/efectos de los fármacos , Adulto , Vacunas contra Hepatitis B/inmunología , Vacunas contra Hepatitis B/administración & dosificación , Femenino , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Masculino , Formación de Anticuerpos/inmunología , Combinación de Medicamentos , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis B/inmunología , Escualeno/administración & dosificación , Escualeno/inmunología , Polisorbatos/administración & dosificación , Hepatitis B/prevención & control , Hepatitis B/inmunología , Inmunogenicidad Vacunal , Lípido A/análogos & derivados , Saponinas , alfa-TocoferolRESUMEN
BACKGROUND: Group A Streptococcus (Strep A) causes both uncomplicated and severe invasive infections, as well as the post-infection complications acute rheumatic fever and rheumatic heart disease. Despite the high global burden of disease resulting from Strep A infections, there is not a licensed vaccine. A 30-valent M protein-based vaccine has previously been shown to be immunogenic in animal models and in a Phase I clinical trial (NCT02564237). Here, we assessed the immunogenicity of a 30-valent messenger (m)RNA vaccine designed to express the same M peptide targets as the 30-valent protein vaccine and compared it with the protein vaccine. METHODS: Female New Zealand white rabbits were immunized with one of four vaccine formulations (3 doses of each formulation at days 1, 28, and 56): soluble mRNA (100 µg/animal), C-terminal transmembrane mRNA (100 µg/animal), protein vaccine (400 µg/animal), or a non-translatable RNA control (100 µg/animal). Serum was collected one day prior to the first dose and on days 42 and 70. Rabbit serum samples were assayed for antibody levels against synthetic M peptides by ELISA. HL-60 opsonophagocytic killing (OPK) assays were performed to assess functional antibody levels. RESULTS: Serum IgG levels were similar for the mRNA and protein vaccines. The CtTM version of the mRNA vaccine elicited slightly higher antibody levels than the mRNA designed to express soluble proteins. OPK activity was similar for the mRNA and protein vaccines, regardless of M type. CONCLUSIONS: The total antibody responses and functional antibody levels elicited by the 30-valent mRNA Strep A vaccines were similar to those observed following immunization with the analogous protein vaccine. The mRNA vaccine platform provides potential advantages to protein-based vaccines including inherent adjuvant activity, increased production efficiency, lower cost, and the potential to rapidly change epitopes/peptides, all of which are important considerations related to multivalent Strep A vaccine development.
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Anticuerpos Antibacterianos , Antígenos Bacterianos , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus pyogenes , Animales , Conejos , Femenino , Vacunas Estreptocócicas/inmunología , Vacunas Estreptocócicas/administración & dosificación , Vacunas Estreptocócicas/genética , Anticuerpos Antibacterianos/sangre , Anticuerpos Antibacterianos/inmunología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Streptococcus pyogenes/inmunología , Streptococcus pyogenes/genética , Inmunogenicidad Vacunal , Proteínas de la Membrana Bacteriana Externa/inmunología , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Portadoras/inmunología , Proteínas Portadoras/genética , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , ARN Mensajero/genética , ARN Mensajero/inmunologíaRESUMEN
The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group evaluates the safety and other key features of new platform technology vaccines, including nucleic acid (RNA and DNA) vaccines. This manuscript uses the BRAVATO template to report the key considerations for a benefit-risk assessment of the coronavirus disease 2019 (COVID-19) mRNA-based vaccine BNT162b2 (Comirnaty®, or Pfizer-BioNTech COVID-19 vaccine) including the subsequent Original/Omicron BA.1, Original/Omicron BA.4-5 and Omicron XBB.1.5 variant-adapted vaccines developed by BioNTech and Pfizer to protect against COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Initial Emergency Use Authorizations or conditional Marketing Authorizations for the original BNT162b2 vaccine were granted based upon a favorable benefit-risk assessment taking into account clinical safety, immunogenicity, and efficacy data, which was subsequently reconfirmed for younger age groups, and by real world evidence data. In addition, the favorable benefit-risk assessment was maintained for the bivalent vaccines, developed against newly arising SARS-CoV-2 variants, with accumulating clinical trial data.
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Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunas de ARNm , Humanos , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Vacuna BNT162/inmunología , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Medición de Riesgo , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/inmunología , Inmunogenicidad VacunalRESUMEN
Filoviruses, like the Marburg (MARV) and Ebola (EBOV) viruses, have caused outbreaks associated with significant hemorrhagic morbidity and high fatality rates. Vaccines offer one of the best countermeasures for fatal infection, but to date only the EBOV vaccine has received FDA licensure. Given the limited cross protection between the EBOV vaccine and Marburg hemorrhagic fever (MHF), we analyzed the protective efficacy of a similar vaccine, rVSV-MARV, in the lethal cynomolgus macaque model. NHPs vaccinated with a single dose (as little as 1.6 × 107 pfu) of rVSV-MARV seroconverted to MARV G-protein prior to challenge on day 42. Vaccinemia was measured in all vaccinated primates, self-resolved by day 14 post vaccination. Importantly, all vaccinated NHPs survived lethal MARV challenge, and showed no significant alterations in key markers of morbid disease, including clinical signs, and certain hematological and clinical chemistry parameters. Further, apart from one primate (from which tissues were not collected and no causal link was established), no pathology associated with Marburg disease was observed in vaccinated animals. Taken together, rVSV-MARV is a safe and efficacious vaccine against MHF in cynomolgus macaques.
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Macaca fascicularis , Enfermedad del Virus de Marburg , Marburgvirus , Vesiculovirus , Vacunas Virales , Animales , Enfermedad del Virus de Marburg/prevención & control , Enfermedad del Virus de Marburg/inmunología , Enfermedad del Virus de Marburg/virología , Marburgvirus/inmunología , Marburgvirus/genética , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Vacunas Virales/genética , Vesiculovirus/genética , Vesiculovirus/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Modelos Animales de Enfermedad , Vacunación , Masculino , Femenino , Eficacia de las Vacunas , Vectores Genéticos , Inmunogenicidad VacunalRESUMEN
Entamoeba histolytica, the causative agent of amebiasis, is one of the top three parasitic causes of mortality worldwide. However, no vaccine exists against amebiasis. Using a lead candidate vaccine containing the LecA fragment of Gal-lectin and GLA-3M-052 liposome adjuvant, we immunized rhesus macaques via intranasal or intramuscular routes. The vaccine elicited high-avidity functional humoral responses as seen by the inhibition of amebic attachment to mammalian target cells by plasma and stool antibodies. Importantly, antigen-specific IFN-γ-secreting peripheral blood mononuclear cells (PBMCs) and IgG/IgA memory B cells (BMEM) were detected in immunized animals. Furthermore, antigen-specific antibody and cellular responses were maintained for at least 8 months after the final immunization as observed by robust LecA-specific BMEM as well as IFN-γ+ PBMC responses. Overall, both intranasal and intramuscular immunizations elicited a durable and functional response in systemic and mucosal compartments, which supports advancing the LecA+GLA-3M-052 liposome vaccine candidate to clinical testing.
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Administración Intranasal , Anticuerpos Antiprotozoarios , Entamoeba histolytica , Entamebiasis , Interferón gamma , Leucocitos Mononucleares , Liposomas , Macaca mulatta , Vacunas Antiprotozoos , Animales , Entamoeba histolytica/inmunología , Liposomas/inmunología , Liposomas/administración & dosificación , Vacunas Antiprotozoos/inmunología , Vacunas Antiprotozoos/administración & dosificación , Anticuerpos Antiprotozoarios/sangre , Anticuerpos Antiprotozoarios/inmunología , Leucocitos Mononucleares/inmunología , Entamebiasis/prevención & control , Entamebiasis/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Inyecciones Intramusculares , Inmunogenicidad Vacunal , Adyuvantes de Vacunas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Linfocitos B/inmunología , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Antígenos de Protozoos/inmunología , Inmunidad Humoral , Memoria Inmunológica , Proteínas Protozoarias/inmunologíaRESUMEN
Whole virion inactivated vaccine CoronaVac (C) and Spike (S) mRNA BNT162b2 (B) vaccines differ greatly in their ability to elicit neutralizing antibodies but have somewhat comparable effectiveness in protecting from severe COVID-19. We conducted further analyses for a randomized trial (Cobovax study, NCT05057169) of third dose homologous and heterologous booster vaccination, i.e. four interventions CC-C, CC-B, BB-C and BB-B. Here, we assess vaccine immunogenicity beyond neutralizing function, including S and non-S antibodies with Fc receptor (FcR) binding, antibody avidity and T cell specificity to 6 months post-vaccination. Ancestral and Omicron S-specific IgG and FcR binding are significantly higher by BNT162b2 booster than CoronaVac, regardless of first doses. Nucleocapsid (N) antibodies are only increased in homologous boosted CoronaVac participants (CC-C). CoronaVac primed participants have lower baseline S-specific CD4+ IFNγ+ cells, but are significantly increased by either CoronaVac or BNT162b2 boosters. Priming vaccine content defined T cell peptide specificity preference, with S-specific T cells dominating B primed groups and non-S structural peptides contributing more in C primed groups, regardless of booster type. S-specific CD4+ T cell responses, N-specific antibodies, and antibody effector functions via Fc receptor binding may contribute to protection and compensate for less potent neutralizing responses in CoronaVac recipients.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , Receptores Fc , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas de Productos Inactivados , Vacunas de ARNm , Humanos , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , Receptores Fc/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de ARNm/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Femenino , Inmunización Secundaria , Inmunogenicidad Vacunal , Adulto , Linfocitos T/inmunología , Masculino , Inmunoglobulina G/inmunología , Persona de Mediana EdadRESUMEN
Safe and effective vaccines against COVID-19 for children and adolescents are needed. This international multicenter, randomized, double-blind, placebo-controlled, phase III clinical trial assessed the efficacy, immunogenicity, and safety of CoronaVac® in children and adolescents (NCT04992260). The study was carried out in Chile, South Africa, Malaysia, and the Philippines. The enrollment ran from September 10, 2021 to March 25, 2022. For efficacy assessment, the median follow-up duration from 14 days after the second dose was 169 days. A total of 11,349 subjects were enrolled. Two 3-µg injections of CoronaVac® or placebo were given 28 days apart. The primary endpoint was the efficacy of the CoronaVac®. The secondary endpoints were the immunogenicity and safety. The vaccine efficacy was 21.02% (95% CI: 1.65, 36.67). The level of neutralizing antibody in the vaccine group was significantly higher than that in the placebo group (GMT: 390.80 vs. 62.20, P <0.0001). Most adverse reactions were mild or moderate. All the severe adverse events were determined to be unrelated to the investigational products. In conclusion, in the Omicron-dominate period, a two-dose schedule of 3 µg CoronaVac® was found to be safe and immunogenic, and showed potential against symptomatic COVID-19 in healthy children and adolescents.