RESUMEN
Despite remarkable progress in the treatment of hepatitis C virus (HCV) infection, it remains a significant global health burden, necessitating the development of an effective prophylactic vaccine. This review paper presents the current landscape of HCV vaccine candidates and approaches, including more traditional, based on inactivated virus, and more modern, such as subunit protein, vectored, based on nucleic acids (DNA and mRNA) and virus-like particles. The concept of the HCV vaccine is first put in the context of viral genetic diversity and adaptive responses to HCV infection, an understanding of which is crucial in guiding the development of an effective vaccine against such a complex virus. Because ethical dimensions are also significant in vaccine research, development, and potential deployment, we also address them in this paper. The road to a safe and effective vaccine to prevent HCV infection remains bumpy due to the genetic variation of HCV and its ability to evade immune responses. The progress in cell-culture systems allowed for the production of an inactivated HCV vaccine candidate, which can induce cross-neutralizing antibodies in vitro, but whether this could prevent infection in humans is unknown. Subunit protein vaccine candidates that entered clinical trials elicited HCV-specific humoral and cellular responses, though it remains to be shown whether they translate into effective prevention of HCV infection or progression of infection to a chronic state. Such responses were also induced by a clinically tested vector-based vaccine candidate, which decreased the viral HCV load but did not prevent chronic HCV infection. These disappointments were not readily predicted from preclinical animal studies. The vaccine platforms employing virus-like particles, DNA, and mRNA provide opportunities for the HCV vaccine, but their potential in this context has yet to be shown. Ensuring the designed vaccine is based on conserved epitope(s) and elicits broadly neutralizing immune responses is also essential. Given failures in developing a prophylactic HCV vaccine, it is crucial to continue supporting national strategies, including funding for screening and treatment programs. However, these actions are likely insufficient to permanently control the HCV burden, encouraging further mobilization of significant resources for HCV vaccine research as a missing element in the elimination of viral hepatitis as a global public health.
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Hepacivirus , Hepatitis C , Desarrollo de Vacunas , Vacunas contra Hepatitis Viral , Humanos , Vacunas contra Hepatitis Viral/inmunología , Hepatitis C/prevención & control , Hepatitis C/inmunología , Hepacivirus/inmunología , Hepacivirus/genética , Anticuerpos Neutralizantes/inmunología , Vacunas de Subunidad/inmunología , Animales , Vacunas de Productos Inactivados/inmunologíaRESUMEN
BACKGROUND: Rabbit hemorrhagic disease (RHD) is an acute infectious disease that damages the rabbit industry by producing significant mortality rates in young and adult rabbits. RHD is better controlled by vaccination. OBJECTIVE: The current study's goal was to prepare and evaluate the immuno-enhancing effect of montanide ISA70 and aluminum hydroxide (Al(OH)3) gel incorporated within the inactivated RHDV2 vaccine and assess the vaccine's protective efficacy against the homologous and heterologous local RHDV2 strains in rabbits. METHODS: Inactivated RHDV vaccines were prepared using Montanide ISA70 oil or Al(OH)3 gel adjuvants and submitted to sterility, safety, and potency tests. 200 rabbits were equally divided into 4 groups: G1 (control), G2 (vaccinated with gel-incorporated vaccine), G3 (vaccinated with montanide-incorporated vaccine), and G4 (vaccinated with gel- and montanide-incorporated vaccines). Individual blood samples were collected from one week to six months from all groups. The vaccine's potency was measured by the HI test and protection percentage post challenge. RESULTS: Data revealed slightly increasing HI titer means reaching the 1st peak at 4 weeks post-vaccination (7.33, 7.67, and 7.33 log2 in the 2nd, 3rd, and 4th groups, respectively), then slightly decreasing and peaked again, giving 9.33 log2 for the2nd group at 3 months post-vaccination (MPV), 10.67 log2 for 3rd the group, and 10.33 log2 for the 4th group at 5 months post-vaccination. Titer gradually decreased but remained protective. The protection rate ranged from 80-100% and 80-90% for homologous and heterologous local RHDV2 vaccines, respectively, within 3 weeks and 6 months post-challenge. The montanide oil RHDV2 vaccine induced better protection than the aluminum gel RHDV2 vaccine. CONCLUSION: The results demonstrated evidence of cross-protection between RHDV2 strains. The oil emulsion vaccine induced higher and longer-lasting antibody titers than those obtained with the RHDV2 aluminum gel vaccine.
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Hidróxido de Aluminio , Infecciones por Caliciviridae , Virus de la Enfermedad Hemorrágica del Conejo , Vacunas Virales , Animales , Conejos , Hidróxido de Aluminio/farmacología , Hidróxido de Aluminio/administración & dosificación , Virus de la Enfermedad Hemorrágica del Conejo/inmunología , Vacunas Virales/inmunología , Infecciones por Caliciviridae/veterinaria , Infecciones por Caliciviridae/prevención & control , Geles , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Ácidos Oléicos/farmacología , Ácidos Oléicos/administración & dosificaciónRESUMEN
BACKGROUND: Human adenovirus type 55 (hAd55) infection can lead to acute respiratory diseases that often present with severe symptoms. Despite its persistent prevalence in military camps and communities, there are no commercially available vaccines or vaccine candidates undergoing clinical evaluation; therefore, there is an urgent need to address this. In this study, we evaluated the immunogenicity of inactivated hAd55 isolates and investigated the effects of adjuvants and various immunization intervals. METHODS AND RESULTS: To select a vaccine candidate, four hAd55 strains (6-9, 6-15 (AFMRI 41014), 28-48 (AFMRI 41013), and 12-164 (AFMRI 41012)) were isolated from infected patients in military camps. Sequence analysis revealed no variation in the coding regions of structural proteins, including pentons, hexons, and fibers. Immunization with inactivated hAd55 isolates elicited robust hAd55-specific binding and neutralizing antibody responses in mice, with adjuvants, particularly alum hydroxide (AH), enhancing antibody titers. Co-immunization with AH also induced hAd14-specific neutralizing antibody responses but did not induce hAd11-specific neutralizing antibody responses. Notably, booster immunization administered at a four-week interval resulted in superior immune responses compared with shorter immunization intervals. CONCLUSIONS: Prime-boost immunization with the inactivated hAd55 isolate and an AH adjuvant shows promise as a potential approach for preventing hAd55-induced respiratory disease. Further research is needed to evaluate the efficacy and safety of these vaccine candidates in preventing hAd55-associated respiratory illnesses.
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Adenovirus Humanos , Adyuvantes Inmunológicos , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Inmunización Secundaria , Vacunas de Productos Inactivados , Animales , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Ratones , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Humanos , Adenovirus Humanos/inmunología , Adenovirus Humanos/genética , Adyuvantes Inmunológicos/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Femenino , Vacunas contra el Adenovirus/inmunología , Vacunas contra el Adenovirus/administración & dosificación , Ratones Endogámicos BALB C , Adyuvantes de Vacunas/administración & dosificación , Infecciones por Adenovirus Humanos/inmunología , Infecciones por Adenovirus Humanos/prevención & control , Infecciones por Adenovirus Humanos/virologíaRESUMEN
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
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: The immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and immunisation is variable. OBJECTIVES: To describe the humoral immune response by correlating IgA and IgG antibodies with NAbs titration following CoronaVac® immunisation and an mRNA (Comirnaty®) booster among healthcare workers (HCWs) and to compare the cytokine and interleukin profiles between HCWs vaccinated with CoronaVac and coronavirus disease 2019 (COVID-19) infected patients. METHODS: Samples from 133 HCWs collected at 20 (T1) and 90 (T2) days after CoronaVac immunisation and 15 (T3) days after a booster dose with the Comirnaty vaccine were analysed for IgA and IgG EIA and neutralisation assay. Cytokine levels from vaccinated individuals at T1 day and COVID-19 patients were compared. FINDINGS: Neutralising antibodies (NAbs) were observed in 81.7% of participants at T1, but only 49.2% maintained detectable NAbs after 90 days. The booster dose increased NAbs response in all participants. The cytokines with the highest levels post-vaccination were IL-6 and MCP-1. The MCP-1, IL-18, and IFN- γ levels were higher in COVID-19 patients than in vaccinated HCWs, while IL-22 levels increased in the vaccinated HCWs group. MAIN CONCLUSIONS: The neutralisation titres in the T2 samples decreased, and antibody levels detected at T2 showed a more significant reduction than the neutralisation. The higher IL-22 expression in immunised individuals compared to those with COVID-19 suggests that IL-22 may be beneficial in protecting against severe disease.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Citocinas , Personal de Salud , Inmunización Secundaria , Inmunoglobulina G , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Masculino , Femenino , Anticuerpos Antivirales/sangre , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , SARS-CoV-2/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Persona de Mediana Edad , Citocinas/inmunología , Citocinas/sangre , Inmunoglobulina A/sangre , Inmunoglobulina A/inmunología , Inmunoglobulina A/análisis , Vacunación , Adulto Joven , Inmunidad Humoral/inmunología , Vacunas de Productos InactivadosRESUMEN
To achieve global herd immunity, widespread vaccination is the most effective strategy. Vaccines stimulate the immune system, generating cytokines and chemokines, isotype antibodies, and neutralizing antibodies; all these molecules collectively provide a more comprehensive characterization of the immune response post-vaccination. We conducted a longitudinal study in northwestern Mexico, involving 120 individuals before vaccination and after the first dose of the SARS-CoV-2 vaccine, and 46 individuals after their second dose. Our findings reveal that antibody levels stabilize over time; cytokine levels generally increase following the first dose but decrease after the second dose and higher than normal levels in IgG1 and IgG3 concentrations are present. Most of the innate cytokines determined in this study were higher after the first dose of the vaccine. Regardless of previous infection history, this finding suggests that the first dose of the vaccine is crucial and may stimulate immunity by enhancing the innate immune response. Conversely, increased levels of IL-4, indicative of a Th2 response, were found in individuals without prior exposure to the virus and in those vaccinated with CoronaVac. These results suggest that the immune response to COVID-19 vaccines is multi-faceted, with preexisting immunity potentiating a more robust innate response. Vaccine type plays a critical role, with genetic vaccines favoring a Th1 response and inactivated vaccines like CoronaVac skewing toward a Th2 profile.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacuna BNT162 , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Citocinas , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Masculino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Citocinas/inmunología , Femenino , Adulto , Persona de Mediana Edad , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Vacuna BNT162/inmunología , Vacuna BNT162/administración & dosificación , México , Estudios Longitudinales , ChAdOx1 nCoV-19/inmunología , ChAdOx1 nCoV-19/administración & dosificación , SARS-CoV-2/inmunología , Células Th2/inmunología , Células TH1/inmunología , Inmunoglobulina G/sangre , Vacunación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Adulto Joven , AncianoRESUMEN
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
Bacterial septicemia represents a significant disease affecting cultured grass carp culture, with the primary etiological agent identified as the Gram-negative bacterium Aeromonas veronii. In response to an outbreak of septicemia in Guangzhou, we developed a formaldehyde-inactivated vaccine against an A. veronii strain designated AV-GZ21-2. This strain exhibited high pathogenicity in experimental infections across at all developmental stages of grass carp. Mortality rates for grass carp weighing 15 ± 5 g ranged from 16 % to 92 % at exposure temperatures of 19 °C-34 °C, respectively. The median lethal dose (LD50) for grass carp groups weighing 15 ± 5 g, 60 ± 10 g, 150 ± 30 g and 500 ± 50 g were determined to be 1.43, 2.52, 4.65 and 7.12 × 107(CFU/mL), respectively. We investigated the inactivated vaccine in conbination with aluminum hydroxide gel (AV-AHG), Montanide ISA201VG (AV-201VG), and white oil (AV-WO) adjuvants. This study aimed to optimize inactivation conditions and identify the adjuvant that elicits the most robust immune response. The AV-GZ21-2 inactivated bacterial solution (AV),when combined with various adjuvants, was capable of inducing a strong specific immune response in grass carp. The relative percent survival (RPS) following a lethal challenge with AV-GZ21-2 were 94 % for AV-AHG, 88 % for AV-201VG, 84 % for AV-WO and 78 % for AV alone. The minimum immunization dose of the AV-AHG vaccine was determined to be 6.0 × 107 CFU per fish, providing immunity for a duration of six months with an immune protection level exceeding 75 %. Furthermore, the AV-AHG vaccine demonstrated significant protective efficacy against various epidemic isolates of A. veronii. Consequently, we developed an inactivated vaccine targeting a highly pathogenic strain of A. veronii, incorporating an aluminum hydroxide gel adjuvant, which resulted in high immune protection and a duration of immunity exceeding six months. These findings suggest that the AV-AHG vaccine holds substantial potential for industrial application.
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Adyuvantes Inmunológicos , Aeromonas veronii , Vacunas Bacterianas , Carpas , Enfermedades de los Peces , Infecciones por Bacterias Gramnegativas , Vacunas de Productos Inactivados , Animales , Carpas/microbiología , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/administración & dosificación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Aeromonas veronii/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/inmunología , Virulencia , Adyuvantes Inmunológicos/administración & dosificación , Dosificación Letal Mediana , Temperatura , China/epidemiología , Hidróxido de Aluminio/administración & dosificaciónRESUMEN
Limited data exist on the factors affecting feline rabies vaccination outcomes during primary immunization. This study aimed to assess if specific factors (signalment, vaccination count, vaccine brand, and time since last vaccination) correlated with meeting global antibody titer standards and absolute titers in young cats given monovalent inactivated rabies vaccines. Analyzing a dataset from cats tested before their first annual booster using the FAVN test, logistic and linear regression models were applied. Among 379 cats, 94.2â¯% achieved titers meeting or exceeding the standard threshold (≥0.5 IU/ml). Time since last vaccination proved to be the primary predictor of vaccination success. Cats receiving two vaccinations tended toward higher titers. Age, sex, breed, and vaccine type showed no impact on outcomes. The present study indicates that vaccination failure in young cats is uncommon, and that the time interval from the latest vaccination is the single most important predictor of successful rabies vaccination.
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Anticuerpos Antivirales , Enfermedades de los Gatos , Vacunas Antirrábicas , Rabia , Vacunación , Animales , Gatos , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/inmunología , Rabia/prevención & control , Rabia/veterinaria , Enfermedades de los Gatos/prevención & control , Enfermedades de los Gatos/inmunología , Enfermedades de los Gatos/virología , Anticuerpos Antivirales/sangre , Vacunación/veterinaria , Femenino , Masculino , Virus de la Rabia/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Eficacia de las VacunasRESUMEN
A natural infection or a vaccination can initially prime the immune system to form immunological memory. The immunity engendered by vaccination against COVID-19 versus natural infection with SARS-CoV-2 has not been well studied in the Indian population. In this study, we compared the immunity conferred by COVID-19 vaccines to naturally acquired immunity to SARS-CoV-2 in a South Indian population. We examined binding and neutralizing antibody (NAb) levels against the ancestral and variant lineages and assessed the ex vivo cellular parameters of memory T cells, memory B cells, and monocytes and finally measured the circulating cytokine response. COVID-19 vaccination stimulates heightened levels of IgG antibodies against the original strain of SARS-CoV-2, as well as increased binding to the spike protein and neutralizing antibody levels. This enhanced response extends to variant lineages such as B.1.617.2 (Delta, India), B.1.1.529 (Omicron, India), B.1.351 (Beta, South Africa), and B.1.1.7 (Alpha, UK). COVID-19 vaccination differs from SARS-CoV-2 infection by having increased frequencies of classical memory B cells, activated memory B and plasma cells, CD4/CD8 T cells of effector memory, effector cells, stem cell-like memory T cells, and classical and intermediate monocytes and diminished frequencies of CD4/CD8 T cells of central memory and non-classical monocytes in vaccinated individuals in comparison to those with natural infection. Thus, COVID-19 vaccination is characterized by enhanced humoral responses and robust activation of innate and memory T cell responses in comparison to natural infection in a South Indian population.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , India , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Adulto , Masculino , Femenino , Vacunación , Glicoproteína de la Espiga del Coronavirus/inmunología , Persona de Mediana Edad , Memoria Inmunológica , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Citocinas/inmunología , Células T de Memoria/inmunología , Células B de Memoria/inmunología , Adulto Joven , Monocitos/inmunología , Vacunas de Productos InactivadosRESUMEN
BACKGROUND: Data on the dynamics and persistence of humoral immunity against SARS-CoV-2 after primary vaccination with two-dose inactivated vaccine (CoronaVac) are limited. This study evaluated the sequential effects of prior infection, heterologous boosting with mRNA-1273 (Moderna), and the occurrence of Omicron vaccine-breakthrough infection (VBI) thereafter. METHODS: We evaluated anti-spike IgG (Abbott) and neutralising (cPASS/GenScript) antibody (nAb) titers up to one year after mRNA-1273 boost in two-dose-CoronaVac-primed Indonesian healthcare workers (August 2021-August 2022). We used linear mixed modeling to estimate the rate of change in antibody levels, and logistic regression to examine associations between antibody levels and VBI. RESULTS: Of 138 participants, 52 (37.7%) had a prior infection and 78 (56.5%) received an mRNA-1273 booster. After two-dose CoronaVac, antibody titers had significantly declined within 180 days, irrespective of prior infection. After mRNA-1273 booster, anti-spike IgG (1.47% decline/day) and Omicron B.1.1.529/BA.2 nAbs declined between day 28-90, and IgG titers plateaued between day 90-360. During the BA.1/BA.2 wave (February-March 2022), 34.6% (27/78) of individuals experienced a VBI (median 181 days after mRNA-1273), although none developed severe illness. VBI was associated with low pre-VBI anti-spike IgG and B.1.1.529/BA.2 nAbs, which were restored post-VBI. CONCLUSIONS: mRNA-1273 booster after two-dose CoronaVac did not prevent BA.1/BA.2 VBI. Periodic vaccine boosters may be warranted against emerging SARS-CoV-2 variants.
Asunto(s)
Vacuna nCoV-2019 mRNA-1273 , Anticuerpos Neutralizantes , Anticuerpos Antivirales , Infección Irruptiva , Vacunas contra la COVID-19 , COVID-19 , Inmunización Secundaria , SARS-CoV-2 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Vacuna nCoV-2019 mRNA-1273/inmunología , Vacuna nCoV-2019 mRNA-1273/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Infección Irruptiva/epidemiología , Infección Irruptiva/inmunología , Infección Irruptiva/prevención & control , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Personal de Salud , Inmunoglobulina G/sangre , Indonesia/epidemiología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunación , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificaciónRESUMEN
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.
Asunto(s)
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.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Adolescente , COVID-19/prevención & control , COVID-19/inmunología , Niño , Femenino , Masculino , Método Doble Ciego , Preescolar , Lactante , SARS-CoV-2/inmunología , Anticuerpos Antivirales/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Inmunogenicidad Vacunal , Filipinas , Sudáfrica , Chile , Malasia , Vacunas de Productos InactivadosRESUMEN
Newly synthesized vaccines prepared from formalin-killed bacteria Streptococcus pyogenes were investigated in the current study to evaluate the effectiveness of the newly synthesized vaccine as well as their safety by injected intraperitoneal. The study involved several steps 1st step is the preparation of the vaccine followed by the 2nd step: Evaluate the effectiveness and vaccine safety against pathogenic S. pyogenes through 4 different groups including control (Group I). Group II (Bacterial, infected group), Group III (Vaccine), and the Last group was the challenged group after the vaccination (Vacc + Bac). Different Immunological and biochemical parameters were measured in addition to hematological and histopathological examinations. For example, oxidative/antioxidants, inflammatory biomarkers, fragmentation and cell damage, and finally the histopathological study. The current study showed an increase in all oxidative, inflammatory, and cell damage (DNA fragmentation assays), additionally markedly elevation in histopathological cell damage in the infected group (Group II) compared with the control group. The vaccine and challenged after vaccination group (vaccine + Bacteria), showed great improvement in oxidative biomarkers (LPO) and an increase in antioxidants biomarkers (GSH, SOD, GST, DPPH, ABTS, GR and GPx), Also the inflammation and histopathological examination. The newly synthesized vaccine improved the resistance of Oreochromis niloticus and can be used as a preventive therapy agent for pathogenic bacteria S. pyogenes.
Asunto(s)
Cíclidos , Hígado , Infecciones Estreptocócicas , Vacunas Estreptocócicas , Streptococcus pyogenes , Vacunación , Animales , Streptococcus pyogenes/inmunología , Infecciones Estreptocócicas/prevención & control , Infecciones Estreptocócicas/inmunología , Cíclidos/inmunología , Cíclidos/microbiología , Hígado/microbiología , Hígado/patología , Hígado/metabolismo , Vacunación/métodos , Vacunas Estreptocócicas/inmunología , Formaldehído , Vacunas de Productos Inactivados/inmunología , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Antioxidantes/farmacología , Estrés Oxidativo/efectos de los fármacos , BiomarcadoresRESUMEN
We administered a questionnaire to participants who received different vaccination regimens to evaluate the effectiveness of Ad5-vectored COVID-19 vaccines. The results showed that administration of intramuscular Ad5-nCoV provided 21.32% more protection against SARS-CoV-2 infection than that of the inactivated COVID-19 vaccine in people who had received only one type of COVID-19 vaccine. Furthermore, aerosolized Ad5-nCoV exhibited good protection, whether it was administered as a homologous booster to people vaccinated with the intramuscular Ad5-nCoV or as a heterologous booster to people vaccinated with inactivated COVID-19 vaccines. Our research indicates that Ad5-nCoV is an effective booster. This finding supports the future selection of COVID-19 immunization strategies.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Vacunas de Productos Inactivados , Humanos , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/inmunología , COVID-19/prevención & control , COVID-19/epidemiología , China/epidemiología , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunología , SARS-CoV-2/inmunología , Estudios Retrospectivos , Masculino , Adulto , Femenino , Inmunización Secundaria , Persona de Mediana Edad , Encuestas y Cuestionarios , Vacunación , Anciano , Eficacia de las Vacunas , Aerosoles , Adulto Joven , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunologíaRESUMEN
Visceral Leishmaniasis is a serious public health problem caused by Leishmania species parasites. Approximately 500 thousand people get Visceral Leishmaniasis (VL) every year. An effective and reliable vaccine against the disease has still not been formulated. Choosing the right adjuvant is important to increase immunogenicity in vaccines prepared with total antigens. In this study, we investigate the ideal adjuvant for use in vaccine formulations against VL. For this purpose, Leishmania antigens (FTLA) obtained from L. infantum parasites by the freeze-thaw method and three different adjuvants (alum-saponin and calcium phosphate) were used. The effectiveness of the formulations was investigated in vitro by cell viability analysis and determination of nitric oxide and cytokine production abilities in J774 macrophage cells. According to the study results, it was determined that formulations prepared with calcium phosphate produced 72% more NO and approximately 7.2 times more IL-12 cytokine. The results obtained showed that calcium phosphate salts can be used as ideal adjuvants in vaccine research against leishmaniasis.
Asunto(s)
Antígenos de Protozoos , Leishmania infantum , Vacunas contra la Leishmaniasis , Animales , Ratones , Vacunas contra la Leishmaniasis/inmunología , Leishmania infantum/inmunología , Antígenos de Protozoos/inmunología , Línea Celular , Macrófagos/inmunología , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/administración & dosificación , Óxido Nítrico/metabolismo , Fosfatos de Calcio , Citocinas/metabolismo , Adyuvantes de Vacunas , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/inmunología , Saponinas/farmacología , Compuestos de Alumbre/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , Supervivencia Celular/efectos de los fármacosRESUMEN
OBJECTIVES: This study was to assess the lot-to-lot consistency, immunogenicity and safety of three manufacturing lots of a quadrivalent inactivated influenza vaccine (IIV4). METHODS: A randomized, double-blind, phase IV clinical trial was conducted in healthy children, adolescents and adults aged 9-59 years in Guizhou Province, China. Eligible participants were enrolled and randomized into three groups in a ratio of 1:1:1 to receive a single dose of one of three manufacturing lots of IIV4. Serum samples were collected before and 28 days after vaccination for hemagglutination inhibition (HI) antibody testing. Safety data were collected for up to 28 days after vaccination. The primary objective was to evaluate the lot-to-lot consistency of immune response as assessed by the geometric mean titer (GMT) of HI antibody at 28 days after vaccination. RESULTS: Between November 27, 2022 and December 18, 2022, 1260 eligible participants were enrolled, with similar participant demographics among groups. Immune responses after vaccination were comparable across groups, with the 95% confidence intervals (CIs) of GMT ratios for all 4 strains falling into the equivalence criterion of (0.67, 1.5). The seroconversion rates (SCRs) and seroprotection rates (SPRs) met the US Center or Biologics Evaluation and Research (CBER) criteria for all strains for each lot (lower limit of 95% CI of SCR ≥ 40% and SPR ≥ 70%). The incidences of solicited and unsolicited adverse reactions were similar among three groups, most of which (91.9%) were mild or moderate in severity. A total of 11 serious adverse events were reported during the study, and all were considered unrelated to vaccination. CONCLUSION: The three manufacturing lots of IIV4 demonstrated consistent immunogenicity. IIV4 can elicit satisfactory immune responses for all four strains and no safety concerns were identified. CLINICAL TRIAL REGISTRATION: Identifier No. NCT05512494.
Asunto(s)
Anticuerpos Antivirales , Pruebas de Inhibición de Hemaglutinación , Inmunogenicidad Vacunal , Vacunas contra la Influenza , Gripe Humana , Vacunas de Productos Inactivados , Humanos , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/efectos adversos , Vacunas contra la Influenza/administración & dosificación , Adolescente , Masculino , Femenino , Método Doble Ciego , Niño , Adulto , Adulto Joven , Vacunas de Productos Inactivados/inmunología , Vacunas de Productos Inactivados/efectos adversos , Vacunas de Productos Inactivados/administración & dosificación , Anticuerpos Antivirales/sangre , Gripe Humana/prevención & control , Gripe Humana/inmunología , Persona de Mediana Edad , China , Voluntarios Sanos , Vacunación/métodosRESUMEN
BACKGROUND: To investigate the safety (adverse events [AEs] and post-vaccination multiple sclerosis [MS] activity within 6 weeks), clinical efficacy (protection against coronavirus disease 2019 [COVID-19]), and vaccine-induced humoral immunogenicity (SARS-CoV-2 neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG) of the Sinopharm (BBIBP-CorV) vaccine among people with MS (PwMS) receiving different disease-modifying therapies (DMTs). METHODS: This prospective cohort study was conducted between November 2021 and May 2022. PwMS were followed for six months after the 2nd dose of vaccination. Antibody responses were measured 2-16 weeks after the 2nd dose injection. Multivariate logistic regression was employed to assess the impact of each DMT on dichotomous antibody responses, adjusting for age, sex, MS phenotype, expanded disability status scale, disease duration, and vaccination-antibody titration interval. RESULTS: Among the 261 screened PwMS, 209 (aged 38.23 ± 9.73 years, female: 70.8%; relapsing-remitting MS: 80.4%) were included. The frequencies of experiencing non-serious AEs and post-vaccination MS activity were 66.0% and 4.8%, respectively. Breakthrough COVID-19 infection was observed in 14.8% of the PwMS. A subcohort of 125 PwMS was assessed for antibody responses. Positive neutralizing antibodies, anti-nucleocapsid IgG, and anti-spike IgG were detected in 36.8%, 35.2%, and 52.0% of the PwMS, respectively. Multivariate regression indicated a 96% (OR: 0.04 [95% CI: 0.00, 0.51], P = 0.013), 93% (OR: 0.07 [0.01, 0.64], P = 0.019), and 89% (OR: 0.11 [0.01, 0.96], P = 0.045) reduced odds of positive neutralizing antibody, anti-nucleocapsid IgG, and anti-spike IgG, respectively, among fingolimod-receivers. Additionally, anti-CD20s-receivers had 88% (OR: 0.12 [0.02, 0.85], P = 0.034) lower odds of being positive for anti-nucleocapsid IgG. CONCLUSIONS: BBIBP-CorV appeared to be well tolerated in PwMS, with promising clinical efficacy. However, a suboptimal humoral response was observed in PwMS receiving fingolimod and anti-CD20s. Future research should investigate the relationship between humoral responses and the frequency and severity of COVID-19 infection across various DMTs.