RESUMO
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.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , SARS-CoV-2 , Humanos , Adolescente , COVID-19/prevenção & controle , COVID-19/imunologia , Criança , Feminino , Masculino , Método Duplo-Cego , Pré-Escolar , Lactente , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Imunogenicidade da Vacina , Filipinas , África do Sul , Chile , Malásia , Vacinas de Produtos InativadosRESUMO
Morbillivirus canis (canine distemper virus (CDV)) is recognized as a multihost pathogen responsible for a transmissible disease affecting both domestic and wild animals. A considerable portion of wildlife populations remain unvaccinated due to a lack of safety and immunogenicity data on existing vaccines for the prevention of CDV infection in these species. This review aimed to assess the current state of CDV vaccination research for both domestic and wild animals and to explore novel vaccine candidates through in vivo studies. It also sought to synthesize the scattered information from the extensive scientific literature on CDV vaccine research, identify key researchers in the field, and highlight areas where research on CDV vaccination is lacking. A scoping review was conducted across four databases following the PRISMA-ScR protocol, with information analyzed using absolute and relative frequencies and 95% confidence intervals (CIs) for study number proportions. Among the 2321 articles retrieved, 68 met the inclusion criteria and focused on CDV vaccines in various animal species, such as dogs, ferrets, minks, and mice. Most of the scientific community involved in this research was in the USA, Canada, France, and Denmark. Various vaccine types, including MLV CDV, recombinant virus, DNA plasmids, inactivated CDV, and MLV measles virus (MeV), were identified, along with diverse immunization routes and schedules employed in experimental and commercial vaccines. Safety and efficacy data were summarized. Notably, 37 studies reported postimmunization CDV challenge, primarily in dogs, revealing the survival rates of vaccinated animals. In summary, CDV vaccines generally demonstrate an acceptable safety profile in dogs and show promise as a means of controlling CDV. However, significant gaps in vaccine research persist, particularly concerning wildlife reservoirs, indicating the need for further investigation.
Assuntos
Animais Domésticos , Animais Selvagens , Vírus da Cinomose Canina , Cinomose , Vacinação , Vacinas Virais , Animais , Animais Selvagens/virologia , Vírus da Cinomose Canina/imunologia , Vírus da Cinomose Canina/genética , Vacinas Virais/imunologia , Vacinas Virais/efeitos adversos , Vacinas Virais/administração & dosagem , Cinomose/prevenção & controle , Cinomose/imunologia , Cinomose/virologia , Vacinação/veterinária , Cães , Furões , Camundongos , Imunogenicidade da Vacina , Vison/virologia , Vison/imunologiaRESUMO
Leptospirosis, a neglected zoonotic disease, is caused by pathogenic spirochetes belonging to the genus Leptospira and has one of the highest morbidity and mortality rates worldwide. Vaccination stands out as one of the most effective preventive measures for susceptible populations. Within the outer membrane of Leptospira spp., we find the LIC12287, LIC11711, and LIC13259 lipoproteins. These are of interest due to their surface location and potential immunogenicity. Thorough examination revealed the conservation of these proteins among pathogenic Leptospira spp.; we mapped the distribution of T- and B-cell epitopes along their sequences and assessed the 3D structures of each protein. This information aided in selecting immunodominant regions for the development of a chimeric protein. Through gene synthesis, we successfully constructed a chimeric protein, which was subsequently expressed, purified, and characterized. Hamsters were immunized with the chimeric lipoprotein, formulated with adjuvants aluminum hydroxide, EMULSIGEN®-D, Sigma Adjuvant System®, and Montanide™ ISA206VG. Another group was vaccinated with an inactivated Escherichia coli bacterin expressing the chimeric protein. Following vaccination, hamsters were challenged with a virulent L. interrogans strain. Our evaluation of the humoral immune response revealed the production of IgG antibodies, detectable 28 days after the second dose, in contrast to pre-immune samples and control groups. This demonstrates the potential of the chimeric protein to elicit a robust humoral immune response; however, no protection against challenge was achieved. While this study provides valuable insights into the subject, further research is warranted to identify protective antigens that could be utilized in the development of a leptospirosis vaccine. KEY POINTS: ⢠Several T- and B-cell epitopes were identified in all the three proteins. ⢠Four different adjuvants were used in vaccine formulations. ⢠Immunization stimulated significant levels of IgG2/3 in vaccinated animals.
Assuntos
Anticorpos Antibacterianos , Vacinas Bacterianas , Leptospirose , Lipoproteínas , Animais , Leptospirose/prevenção & controle , Leptospirose/imunologia , Lipoproteínas/imunologia , Lipoproteínas/genética , Vacinas Bacterianas/imunologia , Vacinas Bacterianas/genética , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Cricetinae , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Adjuvantes Imunológicos/administração & dosagem , Imunoglobulina G/sangue , Epitopos de Linfócito T/imunologia , Epitopos de Linfócito T/genética , Leptospira interrogans/imunologia , Leptospira interrogans/genética , Proteínas da Membrana Bacteriana Externa/imunologia , Proteínas da Membrana Bacteriana Externa/genética , Vacinação , Imunidade Humoral , Leptospira/imunologia , Leptospira/genética , Imunogenicidade da VacinaRESUMO
In the Americas, P. vivax is the predominant causative species of malaria, a debilitating and economically significant disease. Due to the complexity of the malaria parasite life cycle, a vaccine formulation with multiple antigens expressed in various parasite stages may represent an effective approach. Based on this, we previously designed and constructed a chimeric recombinant protein, PvRMC-1, composed by PvCyRPA, PvCelTOS, and Pvs25 epitopes. This chimeric protein was strongly recognized by naturally acquired antibodies from exposed population in the Brazilian Amazon. However, there was no investigation about the induced immune response of PvRMC-1. Therefore, in this work, we evaluated the immunogenicity of this chimeric antigen formulated in three distinct adjuvants: Stimune, AddaVax or Aluminum hydroxide (Al(OH)3) in BALB/c mice. Our results suggested that the chimeric protein PvRMC-1 were capable to generate humoral and cellular responses across all three formulations. Antibodies recognized full-length PvRMC-1 and linear B-cell epitopes from PvCyRPA, PvCelTOS, and Pvs25 individually. Moreover, mice's splenocytes were activated, producing IFN-γ in response to PvCelTOS and PvCyRPA peptide epitopes, affirming T-cell epitopes in the antigen. While aluminum hydroxide showed notable cellular response, Stimune and Addavax induced a more comprehensive immune response, encompassing both cellular and humoral components. Thus, our findings indicate that PvRMC-1 would be a promising multistage vaccine candidate that could advance to further preclinical studies.
Assuntos
Anticorpos Antiprotozoários , Antígenos de Protozoários , Vacinas Antimaláricas , Malária Vivax , Camundongos Endogâmicos BALB C , Plasmodium vivax , Proteínas de Protozoários , Animais , Plasmodium vivax/imunologia , Plasmodium vivax/genética , Camundongos , Antígenos de Protozoários/imunologia , Antígenos de Protozoários/genética , Malária Vivax/imunologia , Malária Vivax/prevenção & controle , Anticorpos Antiprotozoários/imunologia , Vacinas Antimaláricas/imunologia , Feminino , Proteínas de Protozoários/imunologia , Proteínas de Protozoários/genética , Epitopos de Linfócito B/imunologia , Epitopos de Linfócito B/genética , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/genética , Modelos Animais de Doenças , Adjuvantes Imunológicos , Imunogenicidade da Vacina , Antígenos de SuperfícieRESUMO
BACKGROUND: AZD2816 is a variant-adapted COVID-19 vaccine that expresses the full-length SARS-CoV-2 beta variant spike protein but is otherwise similar to AZD1222 (ChAdOx1 nCoV-19). This study aimed to evaluate the safety and immunogenicity of AZD1222 or AZD2816 (or both) primary-series vaccination in a cohort of adult participants who were previously unvaccinated. METHODS: In this phase 2/3, randomised, multinational, active-controlled, non-inferiority, immunobridging study, adult participants previously unvaccinated for COVID-19 were enrolled at 16 study sites in Brazil, South Africa, Poland, and the UK. Participants were stratified by age, sex, and comorbidity and randomly assigned 5:5:5:2 to receive a primary series of AZD1222 (AZD1222 group), AZD2816 (AZD2816 [4-week] group), or AZD1222-AZD2816 (AZD1222-AZD2816 group) at 4-week dosing intervals, or AZD2816 at a 12-week interval (AZD2816 [12-week] group) and evaluated for safety and immunogenicity through 180 days after dose 2. Primary outcomes were safety (rates of solicited adverse events occurring during 7 days and unsolicited adverse events occurring during 28 days after each dose) and immunogenicity (non-inferiority of pseudovirus neutralising antibody geometric mean titre [GMT], GMT ratio margin of 0·67, and seroresponse rate, rate difference margin of -10%, recorded 28 days after dose 2 with AZD2816 [4-week interval] against beta vs AZD1222 against ancestral SARS-CoV-2) in participants who were seronegative at baseline. This trial is registered with ClinicalTrials.gov, NCT04973449, and is completed. FINDINGS: Between July 7 and Nov 12, 2021, 1449 participants were assigned to the AZD1222 group (n=413), the AZD2816 (4-week) group (n=415), the AZD1222-AZD2816 group (n=412), and the AZD2816 (12-week) group (n=209). Ten (2·6%) of 378 participants who were seronegative at baseline in the AZD1222 group, nine (2·4%) of 379 in the AZD2816 (4-week) group, eight (2·1%) of 380 in the AZD1222-AZD2816 group, and 11 (5·8%) of 191 in the AZD2816 (12-week) group had vaccine-related unsolicited adverse events. Serious adverse events were recorded in one (0·3%) participant in the AZD1222 group, one (0·3%) in the AZD2816 (4-week) group, two (0·5%) in the AZD1222-AZD2816 group, and none in the AZD2816 (12-week) group. Co-primary immunogenicity endpoints were met: neutralising antibody GMT (ratio 1·19 [95% CI 1·08-1·32]; lower bound greater than 0·67) and seroresponse rate (difference 1·7% [-3·1 to 6·5]; lower bound greater than -10%) at 28 days after dose 2 were non-inferior in the AZD2816 (4-week) group against beta versus in the AZD1222 group against ancestral SARS-CoV-2. Seroresponse rates were highest with AZD2816 against beta (12-week interval 94·3% [95% CI 89·4-97·3]; 4-week interval 85·7% [81·5-89·2]) and with AZD1222 (84·6% [80·3-88·2]) against ancestral SARS-CoV-2. INTERPRETATION: Primary series of AZD1222 and AZD2816 were well tolerated, with no emergent safety concerns. Both vaccines elicited robust immunogenicity against beta and ancestral SARS-CoV-2 with greater responses demonstrated when testing against SARS-CoV-2 strains that matched those targeted by the respective vaccine. These findings demonstrate the continued importance of ancestral COVID-19 vaccines in protecting against severe COVID-19 and highlight the feasibility of using the ChAdOx1 platform to develop COVID-19 vaccines against future SARS-CoV-2 variants. FUNDING: AstraZeneca.
Assuntos
Vacinas contra COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Imunogenicidade da Vacina , SARS-CoV-2 , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Método Duplo-Cego , COVID-19/prevenção & controle , COVID-19/imunologia , Reino Unido , SARS-CoV-2/imunologia , Brasil , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/administração & dosagem , África do Sul , Polônia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/sangue , Idoso , Vacinação/métodos , Adulto JovemRESUMO
Neosporosis is the major infectious cause of abortion and reproductive losses in cattle worldwide; however, there are no available vaccines or drugs to control this disease. Recently, a dual (positive and negative) DIVA-like (Differentiation of Infected from Vaccinated Animals) vaccine was evaluated in a pregnant mouse model of neosporosis, showing promising immunogenic and protective results. The current report aimed to study the safety, the dose-dependent immunogenicity and the dual DIVA-like character of a recombinant subunit vaccine composed of the major surface antigen from Neospora caninum (rNcSAG1) and the carrier/adjuvant Heat shock protein 81.2 from Arabidopsis thaliana (rAtHsp81.2) in cattle. Healthy heifers were separated and assigned to experimental groups A-F and subcutaneously immunized with 2 doses of vaccine formulations 30 days apart as follows: A (n = 4): 50 µg rNcSAG1 + 150 µg rAtHsp81.2; B (n = 4): 200 µg rNcSAG1 + 600 µg rAtHsp81.2; C (n = 4): 500 µg rNcSAG1 + 1,500 µg rAtHsp81.2; D (n = 3): 150 µg rAtHsp81.2; E (n = 3):1,500 µg rAtHsp81.2, and F (n = 3) 2 ml of sterile PBS. The immunization of heifers with the different vaccine or adjuvant doses (groups A-E) was demonstrated to be safe and did not modify the mean value of the evaluated serum biomarkers of metabolic function (GOT/ASP, GPT/ALT, UREA, Glucose and total proteins). The kinetics and magnitude of the immune responses were dose-dependent. The higher dose of the vaccine formulation (group C) stimulated a broad and potent humoral and cellular immune response, characterized by an IgG1/IgG2 isotype profile and IFN-γ secretion. In addition, this was the first time that dual DIVA-like character of a vaccine against neosporosis was demonstrated, allowing us to differentiate vaccinated from infected heifers by two different DIVA compliant test approaches. These results encourage us to evaluate its protective efficacy in infected pregnant cattle in the future.
Assuntos
Doenças dos Bovinos , Coccidiose , Neospora , Vacinas Protozoárias , Vacinas Sintéticas , Animais , Bovinos , Coccidiose/prevenção & controle , Coccidiose/veterinária , Coccidiose/imunologia , Doenças dos Bovinos/prevenção & controle , Doenças dos Bovinos/imunologia , Doenças dos Bovinos/parasitologia , Neospora/imunologia , Feminino , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Protozoárias/imunologia , Vacinas Protozoárias/administração & dosagem , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Proteínas de Protozoários/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/administração & dosagem , Imunogenicidade da Vacina , GravidezRESUMO
Vaccination is one of the most effective prophylactic public health interventions for the prevention of infectious diseases such as coronavirus disease (COVID-19). Considering the ongoing need for new COVID-19 vaccines, it is crucial to modify our approach and incorporate more conserved regions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to effectively address emerging viral variants. The nucleocapsid protein is a structural protein of SARS-CoV-2 that is involved in replication and immune responses. Furthermore, this protein offers significant advantages owing to the minimal accumulation of mutations over time and the inclusion of key T-cell epitopes critical for SARS-CoV-2 immunity. A novel strategy that may be suitable for the new generation of vaccines against COVID-19 is to use a combination of antigens, including the spike and nucleocapsid proteins, to elicit robust humoral and potent cellular immune responses, along with long-lasting immunity. The strategic use of multiple antigens aims to enhance vaccine efficacy and broaden protection against viruses, including their variants. The immune response against the nucleocapsid protein from other coronavirus is long-lasting, and it can persist up to 11 years post-infection. Thus, the incorporation of nucleocapsids (N) into vaccine design adds an important dimension to vaccination efforts and holds promise for bolstering the ability to combat COVID-19 effectively. In this review, we summarize the preclinical studies that evaluated the use of the nucleocapsid protein as antigen. This study discusses the use of nucleocapsid alone and its combination with spike protein or other proteins of SARS-CoV-2.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus , SARS-CoV-2 , Humanos , Vacinas contra COVID-19/imunologia , SARS-CoV-2/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Proteínas do Nucleocapsídeo de Coronavírus/genética , Imunogenicidade da Vacina , Animais , Fosfoproteínas/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Epitopos de Linfócito T/imunologia , Anticorpos Antivirais/imunologia , Proteínas do Nucleocapsídeo/imunologiaRESUMO
INTRODUCTION: The aim of this study was to evaluate the adverse effects and immune response associated with IgG anti S1 SAEA-CoV-2 antibodies among healthcare workers at Señor del Milagro Hospital in Salta city, after receiving two doses of COVID-19 vaccine. METHODS: A prospective cohort study was carried out from March 2021 to April 2022. Demographic, clinical data, adverse events supposedly attributed to vaccination (AEFIs) were collected and two samples were taken to measure serum antibody levels. RESULTS: 408 volunteers participated, 401 (98%) were vaccinated with Sputnik-V. The average age was 45.5 years with a predominance of the female sex (71%). AEFIs were reported in 188 (46.1%) and 121 (29.7%) after the first and second doses respectively (p<0.001). These events were mostly mild and transient, more frequent after the first dose. The first antibody test was positive in 99% with a mean titer of 9.7 (SD 3.7). The second dosage was positive in 88% with a mean titer of 6.4 (SD 4.4). Participants with a history of infection and previous positive testing showed significantly higher antibody titers (p<0.001). CONCLUSION: The AEFIs reported were mostly mild and transient. Mass vaccination and administration of the recommended dose are essential to achieve effective herd immunity. The majority of vaccinated healthcare workers developed antibodies and those who had the disease prior to vaccination had significant antibody titers.
Introducción: El objetivo de este estudio fue evaluar los efectos adversos y la respuesta inmune de anticuerpos IgG anti S1 SAEA-CoV-2 en el personal de Salud del Hospital del Milagro de la ciudad de Salta, posterior a recibir dos dosis de vacuna COVID-19. Métodos: Se realizó un estudio prospectivo de cohorte desde marzo de 2021 hasta abril 2022. Se recopilaron datos demográficos, clínicos, eventos adversos supuestamente atribuidos a la vacunación (ESAVI) y se tomaron dos muestras de sangre para medir los niveles de anticuerpos. Resultados: Participaron 408 voluntarios, 401 (98%) fueron vacunados con Sputnik- V. La edad promedio fue de 45.5 años con predominio del sexo femenino (71%). Los ESAVI fueron reportados en 188 (46.1%) y 121 (29.7%) luego de la primera y segunda dosis respectivamente (p<0.001). Estos eventos fueron mayormente de carácter leve y transitorios, más frecuentes luego de la primera dosis. El primer dosaje de anticuerpos fue positivo en 99% con una media de títulos de 9.7 (SD 3.7). El segundo dosaje fue positivo en 88% con una media de títulos de 6.4 (SD 4.4). Los participantes con antecedentes de infección y dosajes previos positivos mostraron títulos significativamente más altos de anticuerpos (p<0.001). Conclusión: Los ESAVI reportados fueron mayoritariamente leves y transitorios. La vacunación masiva y la administración de la dosis recomendada son esenciales para lograr una inmunidad colectiva efectiva. La mayoría de los trabajadores de la salud vacunados desarrollaron anticuerpos y aquellos que cursaron la enfermedad previa a la vacunación presentaron títulos significativos más elevados de anticuerpos.
Assuntos
Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Pessoal de Saúde , SARS-CoV-2 , Humanos , Feminino , Masculino , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/efeitos adversos , Pessoal de Saúde/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , COVID-19/prevenção & controle , COVID-19/imunologia , Adulto , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , Imunoglobulina G/sangue , Imunogenicidade da Vacina/imunologiaRESUMO
BACKGROUND: The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil. METHODS: In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards. RESULTS: Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history-0 (nâ¯=â¯26), 1 (nâ¯=â¯140) or 2 (nâ¯=â¯606) booster vaccinations-were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles. CONCLUSIONS: Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0-2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3â¯months after vaccination. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05812586.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Imunogenicidade da Vacina , SARS-CoV-2 , Humanos , Imunização Secundária/métodos , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , COVID-19/prevenção & controle , COVID-19/imunologia , Masculino , Feminino , Adulto , SARS-CoV-2/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Pessoa de Meia-Idade , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Brasil , Adulto Jovem , Vacinação/métodosRESUMO
Inactivated COVID-19 vaccines data in immunocompromised individuals are scarce. This trial assessed the immunogenicity of two CoronaVac doses and additional BNT162b2 mRNA vaccine doses in immunocompromised (IC) and immunocompetent (H) individuals. Adults with solid organ transplant (SOT), hematopoietic stem cell transplant, cancer, inborn immunity errors or rheumatic diseases were included in the IC group. Immunocompetent adults were used as control group for comparison. Participants received two CoronaVac doses within a 28-day interval. IC received two additional BNT162b2 doses and H received a third BNT162b2 dose (booster). Blood samples were collected at baseline, 28 days after each dose, pre-booster and at the trial end. We used three serological tests to detect antibodies to SARS-CoV-2 nucleocapsid (N), trimeric spike (S), and receptor binding domain (RBD). Outcomes included seroconversion rates (SCR), geometric mean titers (GMT) and GMT ratio (GMTR). A total of 241 IC and 100 H adults participated in the study. After two CoronaVac doses, IC had lower SCR than H: anti-N, 33.3% vs 79%; anti-S, 33.8% vs 86%, and anti-RBD, 48.5% vs 85%, respectively. IC also showed lower GMT than H: anti-N, 2.3 vs 15.1; anti-S, 58.8 vs 213.2 BAU/mL; and anti-RBD, 22.4 vs 168.0 U/mL, respectively. After the 3rd and 4th BNT162b2 doses, IC had significant anti-S and anti-RBD seroconversion, but still lower than H after the 3rd dose. After boosting, GMT increased in IC, but remained lower than in the H group. CoronaVac two-dose schedule immunogenicity was lower in IC than in H. BNT162b2 heterologous booster enhanced immune response in both groups.