RESUMEN
Although the recombinant zoster vaccine (RZV) has demonstrated efficacy in reducing the risk of herpes zoster (HZ) for individuals aged 50 years and older, its effectiveness in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. This study was conducted to assess the effect of RZV on the risk of HZ in COPD patients. A multi-institutional propensity score-matched retrospective cohort study was conducted using the TriNetX Research network, including individuals aged 40 years or older with COPD from January 1, 2018, to December 31, 2022. Patients with a history of HZ or prior zoster vaccination were excluded. The primary outcome was HZ occurrence, with secondary outcomes including severe and nonsevere HZ. After propensity score matching, each 17 431 patients receiving RZV and unvaccinated patients were included. The vaccinated group had a significantly lower risk of HZ compared to the unvaccinated group (HR, 0.62; [95% confidence intervals] 95% CI, 0.51-0.75, p < 0.01). Similar risk reductions were observed for nonsevere HZ (HR, 0.61; 95% CI, 049-0.75, p < 0.01) and severe HZ (HR, 0.53; 95% CI, 0.38-0.73, p < 0.01). Further subgroup analyses demonstrated consistent risk reductions across age (50-59, 60-69, 70-79, and ≥80 years), sex, and comorbidities, except for individual aged 40-49 years. This study confirms the effectiveness of RZV in reducing HZ risk in patients with COPD aged 50 years and older, supporting its administration in this population. However, vaccination rates remain low, highlighting the need for improved vaccination strategies in this high-risk group. Efforts to enhance vaccine uptake are warranted to reduce HZ morbidity.
Asunto(s)
Vacuna contra el Herpes Zóster , Herpes Zóster , Puntaje de Propensión , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Femenino , Anciano , Herpes Zóster/prevención & control , Estudios Retrospectivos , Persona de Mediana Edad , Vacuna contra el Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Anciano de 80 o más Años , Adulto , VacunaciónRESUMEN
Tuberculosis(TB) of the Central nervous system (CNS) is a rare and highly destructive disease. The emergence of drug resistance has increased treatment difficulty, leaving the Bacillus Calmette-Guérin (BCG) vaccine as the only licensed preventative immunization available. This study focused on identifying the epitopes of PknD (Rv0931c) and Rv0986 from Mycobacterium tuberculosis(Mtb) strain H37Rv using an in silico method. The goal was to develop a therapeutic mRNA vaccine for preventing CNS TB. The vaccine was designed to be non-allergenic, non-toxic, and highly antigenic. Codon optimization was performed to ensure effective translation in the human host. Additionally, the secondary and tertiary structures of the vaccine were predicted, and molecular docking with TLR-4 was carried out. A molecular dynamics simulation confirmed the stability of the complex. The results indicate that the vaccine structure shows effectiveness. Overall, the constructed vaccine exhibits ideal physicochemical properties, immune response, and stability, laying a theoretical foundation for future laboratory experiments.
Asunto(s)
Simulación por Computador , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Mycobacterium tuberculosis , Tuberculosis del Sistema Nervioso Central , Humanos , Mycobacterium tuberculosis/inmunología , Tuberculosis del Sistema Nervioso Central/prevención & control , Tuberculosis del Sistema Nervioso Central/inmunología , Vacunas contra la Tuberculosis/inmunología , Epítopos/inmunología , Epítopos/química , Vacunas de ARNm , Vacunas Sintéticas/inmunologíaAsunto(s)
Adenoviridae , Leishmania infantum , Leishmaniasis Visceral , Leishmania infantum/inmunología , Leishmania infantum/genética , Animales , Leishmaniasis Visceral/prevención & control , Leishmaniasis Visceral/inmunología , Adenoviridae/genética , Adenoviridae/inmunología , Antígenos de Protozoos/inmunología , Antígenos de Protozoos/genética , Modelos Animales de Enfermedad , Vacunas contra la Leishmaniasis/inmunología , Humanos , Vacunación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificaciónRESUMEN
SpikoGen® vaccine is a subunit COVID-19 vaccine composed of an insect cell expressed recombinant spike protein extracellular domain formulated with Advax-CpG55.2™ adjuvant. A randomized double-blind, placebo-controlled Phase II clinical trial was conducted in 400 adult subjects who were randomized 3:1 to receive two intramuscular doses three weeks apart of either SpikoGen® vaccine 25 µg or saline placebo, as previously reported. This study reports a post hoc analysis of the trial data to explore potential immune correlates of SpikoGen® vaccine protection. A range of humoral markers collected pre- and post-vaccination, including spike- and RBD-binding IgG and IgA, surrogate (sVNT), and conventional (cVNT) virus neutralization tests were compared between participants who remained infection-free or got infected over three months of follow-up. From 2 weeks after the second vaccine dose, 21 participants were diagnosed with SARS-CoV-2 infection, 13 (4.2%) in the SpikoGen® group and 8 (9%) in the placebo group. Those in the vaccinated group who experienced breakthrough infections had significantly lower sVNT titers (GMT 5.75 µg/mL, 95% CI; 3.72-8.91) two weeks after the second dose (day 35) than those who did not get infected (GMT 21.06 µg/mL, 95% CI; 16.57-26.76). Conversely, those who did not develop SARS-CoV-2 infection during follow-up had significantly higher baseline sVNT, cVNT, spike-binding IgG and IgA, and RBD-binding IgG, consistent with a past SARS-CoV-2 infection. SpikoGen® further reduced the risk of re-infection (OR 0.29) in baseline seropositive (previously infected) as well as baseline seronegative participants. This indicates that while SpikoGen vaccine is protective in seronegative individuals, those with hybrid immunity have the most robust protection.
Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Humanos , Glicoproteína de la Espiga del Coronavirus/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/virología , SARS-CoV-2/inmunología , Femenino , Masculino , Adulto , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Persona de Mediana Edad , Método Doble Ciego , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/inmunología , Inmunoglobulina A/sangre , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Adyuvantes de Vacunas , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Adyuvantes Inmunológicos/administración & dosificación , AncianoRESUMEN
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.
Asunto(s)
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
Recombinant influenza virus neuraminidase (NA) is a promising broadly protective influenza vaccine candidate. However, the recombinant protein alone is not sufficient to induce durable and protective immune responses and requires the coadministration of immunostimulatory molecules. Here, we evaluated the immunogenicity and cross-protective potential of a recombinant influenza virus N2 neuraminidase vaccine construct, adjuvanted with a toll-like receptor 9 (TLR9) agonist (CpG 1018® adjuvant), and alum. The combination of CpG 1018 adjuvant and alum induced a balanced and robust humoral and T-cellular immune response against the NA, which provided protection and reduced morbidity against homologous and heterologous viral challenges in mouse and hamster models. This study supports Syrian hamsters as a useful complementary animal model to mice for pre-clinical evaluation of influenza virus vaccines.
Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antivirales , Vacunas contra la Influenza , Neuraminidasa , Infecciones por Orthomyxoviridae , Animales , Vacunas contra la Influenza/inmunología , Vacunas contra la Influenza/administración & dosificación , Neuraminidasa/inmunología , Neuraminidasa/genética , Infecciones por Orthomyxoviridae/prevención & control , Infecciones por Orthomyxoviridae/inmunología , Ratones , Adyuvantes Inmunológicos/administración & dosificación , Femenino , Cricetinae , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Adyuvantes de Vacunas , Ratones Endogámicos BALB C , Protección Cruzada/inmunología , Mesocricetus , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Compuestos de Alumbre/administración & dosificación , Modelos Animales de Enfermedad , Inmunidad CelularRESUMEN
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.
Asunto(s)
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
Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed a lymphoid organ-chip (LO chip) model based on a microfluidic chip seeded with human PBMC at high density within a 3D collagen matrix. Perfusion of the SARS-CoV-2 spike protein mimicked a vaccine boost by inducing a massive amplification of spike-specific memory B cells, plasmablast differentiation, and spike-specific antibody secretion. Features of lymphoid tissue, including the formation of activated CD4+ T cell/B cell clusters and the emigration of matured plasmablasts, were recapitulated in the LO chip. Importantly, myeloid cells were competent at capturing and expressing mRNA vectored by lipid nanoparticles, enabling the assessment of responses to mRNA vaccines. Comparison of on-chip responses to Wuhan monovalent and Wuhan/Omicron bivalent mRNA vaccine boosts showed equivalent induction of Omicron neutralizing antibodies, pointing at immune imprinting as reported in vivo. The LO chip thus represents a versatile platform suited to the preclinical evaluation of vaccine-boosting strategies.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Células B de Memoria , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas de ARNm , Humanos , Vacunas contra la COVID-19/inmunología , Vacunas de ARNm/inmunología , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Células B de Memoria/inmunología , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Tejido Linfoide/inmunología , Dispositivos Laboratorio en un Chip , Vacunas Sintéticas/inmunología , ARN Mensajero/genética , ARN Mensajero/inmunología , ARN Mensajero/metabolismo , Linfocitos B/inmunología , Linfocitos T CD4-Positivos/inmunología , Liposomas , NanopartículasRESUMEN
BACKGROUND: Herpes simplex virus type 1 (HSV-1) is a major cause of viral encephalitis, genital mucosal infections, and neonatal infections. Lactococcus lactis (L. lactis) has been proven to be an effective vehicle for delivering protein antigens and stimulating both mucosal and systemic immune responses. In this study, we constructed a recombinant L. lactis system expressing the protective antigen glycoprotein D (gD) of HSV-1. RESULTS: To improve the stability and persistence of antigen stimulation of the local mucosa, we inserted the immunologic adjuvant interleukin (IL)-2 and the Fc fragment of IgG into the expression system, and a recombinant L. lactis named NZ3900-gD-IL-2-Fc was constructed. By utilizing this recombinant L. lactis strain to elicit an immune response and evaluate the protective effect in mice, the recombinant L. lactis vaccine induced a significant increase in specific neutralizing antibodies, IgG, IgA, interferon-γ, and IL-4 levels in the serum of mice. Furthermore, in comparison to the mice in the control group, the vaccine also enhanced the proliferation levels of lymphocytes in response to gD. Moreover, recombinant L. lactis expressing gD significantly boosted nonspecific immune reactions in mice through the activation of immune-related genes. Furthermore, following the HSV-1 challenge of the murine lung mucosa, mice inoculated with the experimental vaccine exhibited less lung damage than control mice. CONCLUSION: Our study presents a novel method for constructing a recombinant vaccine using the food-grade, non-pathogenic, and non-commercial bacterium L. lactis. The findings indicate that this recombinant vaccine shows promise in preventing HSV-1 infection in mice.
Asunto(s)
Herpes Simple , Herpesvirus Humano 1 , Lactococcus lactis , Ratones Endogámicos BALB C , Lactococcus lactis/genética , Animales , Ratones , Herpesvirus Humano 1/inmunología , Herpesvirus Humano 1/genética , Herpes Simple/prevención & control , Herpes Simple/inmunología , Femenino , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas Sintéticas/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunologíaRESUMEN
Bacille Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis (TB). While BCG protects against TB in children, its protection against pulmonary TB in adults is suboptimal, and the development of a better TB vaccine is a global health priority. Previously, we reported two recombinant BCG strains effective against murine TB with low virulence and lung pathology in immunocompromised mice and guinea pigs. We have recently combined these two recombinant BCG strains into one novel vaccine candidate (BCGΔBCG1419c::ESAT6-PE25SS) and evaluated its immunogenicity, efficacy and safety profile in mice. This new vaccine candidate is non-inferior to BCG in protection against TB, presents reduced pro-inflammatory immune responses and displays an enhanced safety profile.
Asunto(s)
Vacuna BCG , Huésped Inmunocomprometido , Vacunas Sintéticas , Animales , Vacuna BCG/inmunología , Vacuna BCG/efectos adversos , Vacuna BCG/genética , Ratones , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/efectos adversos , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Femenino , Tuberculosis/prevención & control , Tuberculosis/inmunología , Mycobacterium bovis/inmunología , Mycobacterium bovis/genética , Mycobacterium bovis/patogenicidad , Modelos Animales de Enfermedad , Mycobacterium tuberculosis/inmunología , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/patogenicidad , Ratones Endogámicos C57BL , Pulmón/microbiología , Pulmón/patología , Pulmón/inmunología , Tuberculosis Pulmonar/prevención & control , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiología , Eficacia de las VacunasRESUMEN
Background: Echinococcus granulosus is a widespread zoonotic parasitic disease, significantly impacting human health and livestock development; however, no vaccine is currently available for humans. Our preliminary studies indicate that recombinant antigen P29 (rEg.P29) is a promising candidate for vaccine. Methods: Sheep were immunized with rEg.P29, and venous blood was collected at various time points. Serum was isolated, and the presence of specific antibodies was detected using ELISA. We designed and synthesized a total of 45 B cell monopeptides covering rEg.P29 using the overlap method. ELISA was employed to assess the serum antibodies of the immunized sheep for recognition of these overlapping peptides, leading to the preliminary identification of B cell epitopes. Utilizing these identified epitopes, new single peptides were designed, synthesized, and used to optimize and confirm B-cell epitopes. Results: rEg.P29 effectively induces a sustained antibody response in sheep, particularly characterized by high and stable levels of IgG. Eight B-cell epitopes of were identified, which were mainly distributed in three regions of rEg.P29. Finally, three B cell epitopes were identified and optimized: rEg.P2971-90, rEg.P29151-175, and rEg.P29211-235. These optimized epitopes were well recognized by antibodies in sheep and mice, and the efficacy of these three epitopes significantly increased when they were linked in tandem. Conclusion: Three B-cell epitopes were identified and optimized, and the efficacy of these epitopes was significantly enhanced by tandem connection, which indicated the feasibility of tandem peptide vaccine research. This laid a solid foundation for the development of epitope peptide vaccine for Echinococcus granulosus.
Asunto(s)
Anticuerpos Antihelmínticos , Antígenos Helmínticos , Equinococosis , Echinococcus granulosus , Epítopos de Linfocito B , Desarrollo de Vacunas , Animales , Echinococcus granulosus/inmunología , Echinococcus granulosus/genética , Epítopos de Linfocito B/inmunología , Antígenos Helmínticos/inmunología , Antígenos Helmínticos/genética , Ovinos , Equinococosis/prevención & control , Equinococosis/inmunología , Anticuerpos Antihelmínticos/inmunología , Anticuerpos Antihelmínticos/sangre , Enfermedades de las Ovejas/prevención & control , Enfermedades de las Ovejas/inmunología , Enfermedades de las Ovejas/parasitología , Vacunas Sintéticas/inmunología , Proteínas Recombinantes/inmunologíaRESUMEN
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.
Asunto(s)
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.
Asunto(s)
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
Multivalent live-attenuated or inactivated vaccines are often used to control the bovine viral diarrhea disease (BVD). Still, they retain inherent disadvantages and do not provide the expected protection. This study developed a new vaccine prototype, including the external segment of the E2 viral protein from five different subgenotypes selected after a massive screening. The E2 proteins of every subgenotype (1aE2, 1bE2, 1cE2, 1dE2, and 1eE2) were produced in mammalian cells and purified by IMAC. An equimolar mixture of E2 proteins formulated in an oil-in-water adjuvant made up the vaccine candidate, inducing a high humoral response at 50, 100, and 150 µg doses in sheep. A similar immune response was observed in bovines at 50 µg. The cellular response showed a significant increase in the transcript levels of relevant Th1 cytokines, while those corresponding to the Th2 cytokine IL-4 and the negative control were similar. High levels of neutralizing antibodies against the subgenotype BVDV1a demonstrated the effectiveness of our vaccine candidate, similar to that observed in the sera of animals vaccinated with the commercial vaccine. These results suggest that our vaccine prototype could become an effective recombinant vaccine against the BVD.
Asunto(s)
Anticuerpos Antivirales , Diarrea Mucosa Bovina Viral , Vacunas de Subunidad , Vacunas Sintéticas , Vacunas Virales , Animales , Bovinos , Vacunas Virales/inmunología , Vacunas de Subunidad/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Vacunas Sintéticas/inmunología , Diarrea Mucosa Bovina Viral/prevención & control , Diarrea Mucosa Bovina Viral/inmunología , Diarrea Mucosa Bovina Viral/virología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Ovinos , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/genética , Citocinas/metabolismo , Virus de la Diarrea Viral Bovina/inmunología , Virus de la Diarrea Viral Bovina/genética , Virus de la Diarrea Viral Bovina Tipo 1/inmunología , Virus de la Diarrea Viral Bovina Tipo 1/genéticaRESUMEN
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.
Asunto(s)
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
The factors affecting the antibody responses to the ZF2001 vaccine remain unknown. To address this, we conducted a cross-sectional serological study in the real world. Adults with no prior SARS-CoV-2 infection history and received three doses of ZF2001 vaccine were invited to our study in the early stages of the COVID-19 epidemic in Chongqing between 7 April 2021 and 17 November 2021. A questionnaire survey was conducted to obtain demographic characteristics, health information, and the frequency of lifestyles at the time of enrollment. A total of 266 eligible subjects aged 18 to 86 years, with a median age of 56.00 (IQR: 34-66) participated. 68.80% of them were female. Hypertension (13.16%) and diabetes (6.02%) were common comorbidities. Serum samples were collected at one month after the third dose of ZF2001 vaccination, and serological testing was conducted using the Pseudovirus-Based Neutralization Assay. The chi-square test was employed to compare seropositivity rates, and the Mann-Whitney U test or the Kruskal-Wallis test was used to analyze the neutralizing antibodies level in stratified groups. Subsequently, univariate and multivariate linear regression analyses were conducted to identify the influencing factors. We observed that seropositivity rates was 76.32%, with 95% confidence interval (95%CI) 70.85%-81.03%, and geometric mean titer (GMT) was 120.26, with 95%CI 100.38-144.08. Age, diabetes, and frequently of alcohol were negative associations with antibody response (ß = -0.2021, 95% CI: -0.2507 to -0.1535, ß = -0.2873, 95% CI: -0.5590 to -0.0155, ß = -0.2082, 95% CI: -0.3419 to-0.0746, P < 0.0001, P = 0.0384, P = 0.0024). Conversely, the -interval between 1 and 2 dose and frequently of tea were positive associations with antibody response (ß = 0.1369, 95% CI: 0.0463 to 0.2275, ß = 0.0830, 95% CI: 0.0106 to 0.1554, P = 0.0032, P = 0.0247). Overall, the ZF2001 vaccine-induced antibody response was influenced by a multifactor that may provide a reference for the development of personalized antigen vaccines and vaccination strategies in the future.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios Transversales , COVID-19/prevención & control , COVID-19/inmunología , COVID-19/epidemiología , Adulto , Anticuerpos Antivirales/sangre , China/epidemiología , Anciano , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Anticuerpos Neutralizantes/sangre , Adulto Joven , Anciano de 80 o más Años , Adolescente , Vacunación , Formación de Anticuerpos , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Proteínas Recombinantes/inmunologíaRESUMEN
Despite the high efficiency of current SARS-CoV-2 mRNA vaccines in reducing COVID-19 morbidity and mortality, waning immunity and the emergence of resistant variants underscore the need for novel vaccination strategies. This study explores a heterologous mRNA/Modified Vaccinia virus Ankara (MVA) prime/boost regimen employing a trimeric form of the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) protein compared to a homologous MVA/MVA regimen. In C57BL/6 mice, the RBD was delivered during priming via an mRNA vector encapsulated in nanoemulsions (NE) or lipid nanoparticles (LNP), followed by a booster with a replication-deficient MVA-based recombinant virus (MVA-RBD). This heterologous mRNA/MVA regimen elicited strong anti-RBD binding and neutralizing antibodies (BAbs and NAbs) against both the ancestral SARS-CoV-2 strain and different variants of concern (VoCs). Additionally, this protocol induced robust and polyfunctional RBD-specific CD4 and CD8 T cell responses, particularly in animals primed with mLNP-RBD. In K18-hACE2 transgenic mice, the LNP-RBD/MVA combination provided complete protection from morbidity and mortality following a live SARS-CoV-2 challenge compared with the partial protection observed with mNE-RBD/MVA or MVA/MVA regimens. Although the mNE-RBD/MVA regimen only protects half of the animals, it was able to induce antibodies with Fc-mediated effector functions besides NAbs. Moreover, viral replication and viral load in the respiratory tract were markedly reduced and decreased pro-inflammatory cytokine levels were observed. These results support the efficacy of heterologous mRNA/MVA vaccine combinations over homologous MVA/MVA regimen, using alternative nanocarriers that circumvent intellectual property restrictions of current mRNA vaccine formulations.
Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Ratones Endogámicos C57BL , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Virus Vaccinia , Animales , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , SARS-CoV-2/genética , Ratones , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , COVID-19/prevención & control , COVID-19/inmunología , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Neutralizantes/inmunología , Virus Vaccinia/genética , Virus Vaccinia/inmunología , Humanos , Femenino , Nanopartículas/administración & dosificación , Vacunación , Vacunas de ARNm/administración & dosificación , Ratones Transgénicos , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Linfocitos T CD8-positivos/inmunología , Enzima Convertidora de Angiotensina 2/inmunología , Enzima Convertidora de Angiotensina 2/genética , LiposomasRESUMEN
Research has shown that voraxin α derived from male ticks stimulates blood feeding to engorge in female ticks. Whereas, the oviposition rate, egg weight, and body weight of female ticks were reduced in animals vaccinated with recombinant (r-) voraxin α. These data suggest a potential role of r-voraxin α as a functional anti-tick antigen in Rhipicephalus appendiculatus and Amblyomma hebraeum tick infestation. This study investigated the immunogenicity of r-voraxin α protein from Hyalomma anatolicum (H. anatolicum) tick as an anti-tick vaccine in rabbits. The H. anatolicum voraxin α sequence was optimized according to the codon usage in E. coli before being sub-cloned into pQE30. The gene sequence of the voraxin α was synthesized, verified by DNA sequencing, cloned in a pQE30 vector, and transformed into E. coli. Then, the expression of the r-voraxin α protein was confirmed by SDS-PAGE and Western blot analysis. Subsequently, three rabbits were immunized with the r-voraxin α as the vaccinated group, whereas three rabbits without injection were considered the control group. The result indicated the success of cloning of codon-optimized H. anatolicum voraxin α gene. Moreover, the expression of the r-voraxin α protein (approximately 18â¯kDa) in the bacterial expression system was confirmed by SDS-PAGE and Western blot analysis. The results of this study showed that the mortality rate in vaccine recipients increased compared to the control group (P < 0.01). Also, the egg weight, oviposition rate, and engorgement weight of female ticks fed from vaccinated animals were significantly reduced compared to the control group (P < 0.01). The results confirmed that the codon-optimized H. anatolicum voraxin α gene expressed in the bacterial expression system could be a suitable anti-tick vaccine against H. anatolicum tick infestation.
Asunto(s)
Ixodidae , Infestaciones por Garrapatas , Vacunas Sintéticas , Animales , Conejos , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/veterinaria , Infestaciones por Garrapatas/inmunología , Femenino , Vacunas Sintéticas/inmunología , Ixodidae/inmunología , Codón , Masculino , Proteínas Recombinantes/inmunología , Inmunogenicidad Vacunal , Escherichia coli , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/genéticaRESUMEN
Zika virus (ZIKV) infection remains a global public health problem. After the "Public Health Emergencies of International Concern" declared in February 2016, the incidence of new infections by this pathogen has been decreasing in many areas. However, there is still a likely risk that ZIKV will spread to more countries. To date, there is no vaccine or antiviral drug available to prevent or treat Zika virus infection. In the Zika vaccine development, those based on protein subunits are attractive as a non-replicable platform due to their potentially enhanced safety profile to be used in all populations. However, these vaccines frequently require multiple doses and adjuvants to achieve protective immunity. In this study we show the immunological evaluation of new formulations of the recombinant protein ZEC, which combines regions of domain III of the envelope and the capsid from ZIKV. Two nucleotide-based adjuvants were used to enhance the immunity elicited by the vaccine candidate ZEC. ODN 39M or c-di-AMP was incorporated as immunomodulator into the formulations combined with aluminum hydroxide. Following immunizations in immunocompetent BALB/c mice, the formulations stimulated high IgG antibodies. Although the IgG subtypes suggested a predominantly Th1-biased immune response by the formulation including the ODN 39M, cellular immune responses measured by IFNγ secretion from spleen cells after in vitro stimulations were induced by both immunomodulators. These results demonstrate the capacity of both immunomodulators to enhance the immunogenicity of the recombinant subunit ZEC as a vaccine candidate against ZIKV.
Asunto(s)
Adyuvantes Inmunológicos , Anticuerpos Antivirales , Ratones Endogámicos BALB C , Vacunas de Subunidad , Vacunas Sintéticas , Infección por el Virus Zika , Virus Zika , Animales , Virus Zika/inmunología , Vacunas de Subunidad/inmunología , Vacunas de Subunidad/administración & dosificación , Infección por el Virus Zika/prevención & control , Infección por el Virus Zika/inmunología , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Ratones , Femenino , Adyuvantes Inmunológicos/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Virales/inmunología , Vacunas Virales/administración & dosificación , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunogenicidad Vacunal , Anticuerpos Neutralizantes/sangre , Anticuerpos Neutralizantes/inmunología , Adyuvantes de Vacunas , Inmunidad Celular , Proteínas del Envoltorio Viral/inmunología , Proteínas de la Cápside/inmunología , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunologíaRESUMEN
mRNA platform holds promise for next-generation Varicella-zoster Virus (VZV) vaccine development due to its high potency at inducing strong T-cell response. Built upon the design of our 1st-generation VZV mRNA vaccine that encodes for full-length gE antigen, in this study we reported on a novel combinatorial strategy to further optimize the gE-encoding mRNA sequence through signal peptide replacement, C-terminal modification, and insertion of mRNA-stabilizing motif, which collectively contributed to significantly improved vaccine immunogenicity. In adult mice, aged mice, and immunocompromised mice, this optimized VZV mRNA vaccine showed strong superiority in multiple aspects including the induction of gE-specific antibodies, specific memory B-cell response, as well as Th1-type T-cell response.