Protective Immunity of COVID-19 Vaccination with ChAdOx1 nCoV-19 Following Previous SARS-CoV-2 Infection: A Humoral and Cellular Investigation.

Infections caused by SARS-CoV-2 induce a severe acute respiratory syndrome called COVID-19 and have led to more than six million deaths worldwide. Vaccination is the most effective preventative measure, and cellular and humoral immunity is crucial to developing individual protection. Here, we aim to investigate hybrid immunity against SARS-CoV-2 triggered by the ChAadOx1 nCoV-19 vaccine in a Brazilian cohort. We investigated the immune response from ChAadOx1 nCoV-19 vaccination in naïve (noCOVID-19) and previously infected individuals (COVID-19) by analyzing levels of D-dimers, total IgG, neutralizing antibodies (Nabs), IFN-γ (interferon-γ) secretion, and immunophenotyping of memory lymphocytes. No significant differences in D-dimer levels were observed 7 or 15 days after vaccination (DAV). All vaccinated individuals presented higher levels of total IgG or Nabs with a positive correlation (R = 0.88). Individuals in the COVID-19 group showed higher levels of antibody and memory B cells, with a faster antibody response starting at 7 DAV compared to noCOVID-19 at 15 DAV. Further, ChAadOx1 nCoV-19 vaccination led to enhanced IFN-γ production (15 DAV) and an increase in activated T CD4+ naïve cells in noCOVID-19 individuals in contrast with COVID-19 individuals. Hence, our data support that hybrid immunity triggered by ChAadOx1 nCoV-19 vaccination is associated with enhanced humoral response, together with a balanced cellular response.

Exploratory study of humoral and cellular immunity to 17DD Yellow Fever vaccination in children and adults residents of areas without circulation of Yellow Fever Virus.

The present investigation comprised two independent observational arms to evaluate the influence of pre-existing flavivirus humoral immunity and the age-impact on 17DD-YF vaccination immunity. Flavivirus (YFV; DENV; ZIKV) serology and YF-specific cellular immunity was evaluated in 288 children/9Mths-4Yrs and 288 adults/18-49Yrs residents of areas without YFV circulation. Data demonstrated that flavivirus seropositivity at baseline was higher in Adults as compared to Children (26%;87%;67% vs 6%;13%;15%, respectively). The heterologous flavivirus seropositivity (DENV; ZIKV) did not impact the YF-specific cellular immune response at baseline. However, higher levels of NCD4, EMCD8, IFN-MCD8, NCD19 and nCMCD19 were observed in subjects with pre-existing YFV seropositivity. Primary vaccination of YFV-seronegative volunteers led to higher levels of YF-neutralizing antibodies in Adults as compared to Younger Children (9Mths-2Yrs). Although similar seropositivity rates observed amongst Children and Adults at D30-45, lower rates were observed in Younger Children (9Mths-2Yrs) at D365 (94%;95%;100% vs 87%;96%;99%, respectively). A progressive decline in antibody levels were reported at D365, being more expressive in Children as compared to Adults. All age-subgroups exhibited at D30-45 increased levels of eEfCD4, EMCD4, IFN-MCD8 and nCMCD19 together with a decrease of eEfCD8 and CMCD8. While an increase of EMCD8 were observed in all subgroups at D30-45, a declined duration at D365 was reported only in Younger Children (9Mths-2Yrs). Biomarker signatures further support that only Younger Children (9Mths-2Yrs) presented a progressive decline of EMCD8 at D365. Together, these findings demonstrated that regardless the similarities observed in YF-neutralizing antibodies, the age impacts the duration of cellular immune response to primary 17DD-YF vaccination.

Survey on Non-Human Primates and Mosquitoes Does not Provide Evidences of Spillover/Spillback between the Urban and Sylvatic Cycles of Yellow Fever and Zika Viruses Following Severe Outbreaks in Southeast Brazil.

In the last decade, Flaviviruses such as yellow fever (YFV) and Zika (ZIKV) have expanded their transmission areas. These viruses originated in Africa, where they exhibit both sylvatic and interhuman transmission cycles. In Brazil, the risk of YFV urbanization has grown, with the sylvatic transmission approaching the most densely populated metropolis, while concern about ZIKV spillback to a sylvatic cycle has risen. To investigate these health threats, we carried out extensive collections and arbovirus screening of 144 free-living, non-human primates (NHPs) and 5219 mosquitoes before, during, and after ZIKV and YFV outbreaks (2015-2018) in southeast Brazil. ZIKV infection was not detected in any NHP collected at any time. In contrast, current and previous YFV infections were detected in NHPs sampled between 2017 and 2018, but not before the onset of the YFV outbreak. Mosquito pools screened by high-throughput PCR were positive for YFV when captured in the wild and during the YFV outbreak, but were negative for 94 other arboviruses, including ZIKV, regardless of the time of collection. In conclusion, there was no evidence of YFV transmission in coastal southeast Brazil before the current outbreak, nor the spread or establishment of an independent sylvatic cycle of ZIKV or urban Aedes aegypti transmission of YFV in the region. In view of the region's receptivity and vulnerability to arbovirus transmission, surveillance of NHPs and mosquitoes should be strengthened and continuous.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b.

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6% and 98.4% of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100% seroprotection (> or =0.15 microg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 microg/mL, 10.3 microg/mL and 10.3 microg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7%, 100% and 99.9%, respectively, for DTP/Hib-BM, three lots altogether and 99.2%, 100% and 100% for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

Cellular and Molecular Immunology Approaches for the Development of Immunotherapies against the New Coronavirus (SARS-CoV-2): Challenges to Near-Future Breakthroughs

A síndrome respiratória aguda grave causada pelo novo coronavírus (SARS-CoV-2), denominado COVID-19, foi destacada como a doença infecciosa mais importante do nosso tempo, sem vacina e sem tratamento disponível até o momento, com grande impacto nos sistemas de saúde em todo o mundo e com altas taxas de mortalidade associadas a doenças virais respiratórias. As comunidades médica e científica também foram confrontadas com a necessidade urgente de compreender melhor o mecanismo de interação vírus-hospedeiro com o objetivo de desenvolver terapias e vacinas. Uma vez que esta doença viral pode desencadear uma forte resposta imune inata, causando graves danos ao trato pulmonar, imunoterapias também têm sido exploradas como um meio para verificar o efeito imunomodulador e melhorar os resultados clínicos, enquanto a imunologia COVID-19 abrangente ainda permanece sob investigação. Nesta revisão, tanto a imunopatologia celular e molecular quanto os distúrbios hemostáticos induzidos por SARS-CoV-2 são resumidos. As abordagens imunoterapêuticas baseadas nos estudos clínicos e não clínicos mais recentes, enfatizando seus efeitos para o tratamento do COVID-19, também são abordadas. As informações apresentadas elucidam insights úteis com o objetivo de preencher as lacunas de conhecimento em torno de imunoterapias promissoras que tentam controlar a disfunção de fatores do hospedeiro durante o curso desta doença viral infecciosa.

Influência dos polimorfismos nos genes IFNL3 e IFNL4 na resposta virológica sustentada e na produção de citocinas em pacientes brasileiros com hepatite c crônica tratados com alfapeginterferona

A hepatite C crônica (HCC) é um grande problema de Saúde Pública, pois se apresenta como uma doença assintomática, onde 20% irão progredir para cirrose, podendo ainda evoluir para carcinoma hepatocelular. Os polimorfismos de nucleotídeos únicos (SNPs) próximos a região do interferon lambda 3 (IFNL3) são marcadores que estão associados a eliminação espontânea do vírus, e no desfecho dos tratamentos à base de Peg-interferon (Peg-IFN\03B1), bem como, tratamentos recentes com os antivirais de ação direta. Neste estudo, a genotipagem de SNPs na região de IFNL3 e IFNL4 na população Brasileira e seu papel na resposta virológica sustentada (RVS) e na regulação da resposta imunológica sistêmica foram avaliados. Para isso, 740 pacientes com HCC infectados com genótipos virais 1, 2 e 3 tratados com Peg-IFN\03B1 e ribavirina foram recrutados (conforme protocolo do Ministério da Saúde de 2015) as amostras coletadas nos tempos 0, 1ª, 2ª, 3ª, 12ª semanas de tratamento e 3ª semana pós-tratamento, juntamente com 24 amostras de voluntários sadios (0, 24 e 72 horas) que receberam uma dose dos biofármacos. Avaliamos a frequência de 12 SNPs da região gênica do IFNL3 e 4 em pacientes estratificados de acordo com o desfecho. Confirmamos a associação de 10 SNPs com o desfecho favorável do tratamento na população miscigenada brasileira. Dentre estes, destacam-se os SNPs rs12979860, rs8109886 e rs8099917 que, após análises de desequilíbrio de ligação, funcionam como etiquetas de cobertura de toda região Além disso, utilizando a combinação entre os genótipos destes três SNPs preditores aumentou-se a taxa de predição da RVS, independente de outros fatores preditivos do hospedeiro. A partir das amostras de um subgrupo de 24 pacientes e 24 voluntários sadios, foram avaliados níveis séricos de citocinas e quimiocinas bem como a expressão de genes da via de sinalização do IFN tipo I. O perfil observado nos níveis de CCL3, CCL4 e CXCL10 se mostraram bons biomarcadores de RVS. Níveis baixos de CCL4 e CXCL10 foram detectados em pacientes com genótipo rs12979860-CC, favorável a resposta ao tratamento. Apresentaram diferenças significativas entre pacientes homozigotos CC em relação aos pacientes com genótipo TT. Por fim, os pacientes apresentaram o efeito antagônico entre IFN-\03BB e os genes da via dos IFN tipo I, onde níveis altos de expressão de mRNA de IFNL3 e 4 antes do tratamento estavam associados à níveis baixos do IFNA1 nos pacientes com HCC. Genes expressos da via de sinalização do IFN tipo I apresentaram altos níveis antes do início do tratamento, com exceção dos genes IFNA1, IFNAR e IFHI. Em resumo, estes dados sugerem que a combinação de genótipos de rs12979860, rs8109886 e rs80999917 são preditores mais precisos do resultado do tratamento em uma população miscigenada como a Brasileira e que os genótipos do gene IFNL3 e 4 regulam a resposta imuno-inflamatória indicando que os mecanismos genéticos controlam a regulação dos níveis de IFNs tipo I exercido pelos IFNs tipo III.

Comparative analysis of the intracerebral mouse protection test and serological method for potency assays of pertussis component in DTP vaccine

The aim of this study was to compare the PSPT standardized in-house as an alternative to MPT for potency assays of pertussis component. Statistical analyses have showed similar pertussis potency values when PSPT was compared to MPT. Significant correlation between the potency results obtained by in vivo and in vitro assays was also been observed. Results by PSPT have demonstrated reproducibility and accuracy for potency pertussis control and this approach has been considered promising for use at least during the steps of production.

Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM) was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK), which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6 percent and 98.4 percent of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100 percent seroprotection (>0.15 µg/mL) with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT) was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7 percent, 100 percent and 99.9 percent, respectively, for DTP/Hib-BM, three lots altogether and 99.2 percent, 100 percent and 100 percent for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.