Comprehensive landscape of neutralizing antibody and cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF primary vaccination in adults.

The present study aimed at evaluating the YF-specific neutralizing antibody profile besides a multiparametric analysis of phenotypic/functional features of cell-mediated response elicited by the 1/5 fractional dose of 17DD-YF vaccine, administered as a single subcutaneous injection. The immunological parameters of each volunteer was monitored at two time points, referred as: before (Day 0) [Non-Vaccinated, NV(D0)] and after vaccination (Day 30-45) [Primary Vaccinees, PV(D30-45)]. Data demonstrated high levels of neutralizing antibodies for PV(D30-45) leading to a seropositivity rate of 93%. A broad increase of systemic soluble mediators with a mixed profile was also observed for PV(D30-45), with IFN-γ and TNF-α presenting the highest baseline fold changes. Integrative network mapping of soluble mediators showed increased correlation numbers in PV(D30-45) as compared to NV(D0) (532vs398). Moreover, PV(D30-45) exhibited increased levels of Terminal Effector (CD45RA+CCR7-) CD4+ and CD8+ T-cells and Non-Classical memory B-cells (IgD+CD27+). Dimensionality reduction of Mass Cytometry data further support these findings. A polyfunctional cytokine profile (TNF-α/IFN-γ/IL-10/IL-17/IL-2) of T and B-cells was observed upon in vitro antigen recall. Mapping and kinetics timeline of soluble mediator signatures for PV(D30-45) further confirmed the polyfunctional profile upon long-term in vitro culture, mediated by increased levels of IFN-γ and TNF-α along with decreased production of IL-10. These findings suggest novel insights of correlates of protection elicited by the 1/5 fractional dose of 17DD-YF vaccine.

Strategies for expanding childhood vaccination in the Americas following the COVID-19 pandemic.

Objective: To provide an overview of the status of the childhood vaccination schedule in the Americas, outline program structures, and identify updated implementation strategies to improve vaccination coverage following the COVID-19 pandemic. Methods: A group of experts in pediatrics, epidemiology, vaccines, and global and public health discussed the current status of the childhood vaccination schedule in the Americas, describing the program structure and identifying new implementation strategies that have the potential to improve vaccination coverage in the post-pandemic context, after the challenges COVID-19 presented for more than two years. Results: The Americas currently face a high risk of resurgence of diseases that were previously controlled or eliminated. Therefore, it is important to find new strategies to educate citizens on the risks associated with lower vaccination rates, especially in children. Conclusions: New strategies along with strong mobilization of the population and advocacy by citizens are necessary to prevent antivaccination groups from gaining a stronger presence in the region and jeopardizing the credibility of the Expanded Program on Immunization.

Immune response induced by standard and fractional doses of 17DD yellow fever vaccine.

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

Strategies for expanding childhood vaccination in the Americas following the COVID-19 pandemic / Estrategias para ampliar la vacunación infantil en la Región de las Américas después de la pandemia de COVID-19 / Estratégias para ampliar a vacinação infantil nas Américas depois da pandemia de COVID-19

[ABSTRACT]. Objective. To provide an overview of the status of the childhood vaccination schedule in the Americas, outline program structures, and identify updated implementation strategies to improve vaccination coverage following the COVID-19 pandemic. Methods. A group of experts in pediatrics, epidemiology, vaccines, and global and public health discussed the current status of the childhood vaccination schedule in the Americas, describing the program structure and identifying new implementation strategies that have the potential to improve vaccination coverage in the post-pandemic context, after the challenges COVID-19 presented for more than two years. Results. The Americas currently face a high risk of resurgence of diseases that were previously controlled or eliminated. Therefore, it is important to find new strategies to educate citizens on the risks associated with lower vaccination rates, especially in children. Conclusions. New strategies along with strong mobilization of the population and advocacy by citizens are necessary to prevent antivaccination groups from gaining a stronger presence in the region and jeopardizing the credibility of the Expanded Program on Immunization.

[RESUMEN]. Objetivo. Presentar un panorama general de la situación del calendario de vacunación infantil en la Región de las Américas, describir la estructura de los programas y encontrar estrategias actualizadas para su ejecución a fin de mejorar la cobertura de vacunación después de la pandemia de COVID-19. Métodos. Un grupo de expertos en pediatría, epidemiología, vacunas y salud pública y mundial analizó la situación actual del calendario de vacunación infantil en la Región de las Américas, mediante la descripción de la estructura de los programas y la búsqueda de nuevas estrategias de ejecución capaces de mejorar la cobertura de vacunación en el contexto posterior a la pandemia de COVID-19, una vez superados los desafíos planteados por esta durante más de dos años. Resultados. En este momento, en la Región de las Américas hay un riesgo alto de reaparición de enferme- dades previamente controladas o eliminadas. En consecuencia, es importante contar con nuevas estrategias para la educación de salud de la ciudadanía sobre los riesgos asociados a las tasas bajas de vacunación, especialmente en la población infantil. Conclusiones. Es necesario contar con nuevas estrategias, acompañadas de una fuerte movilización de la población y una promoción por parte de la ciudadanía, para evitar que los grupos que generan mensajes antivacunas aumenten su presencia en la Región y pongan en peligro la credibilidad del Programa Ampliado de Inmunización.

[RESUMO]. Objetivo. Apresentar um panorama da situação do calendário de vacinação infantil nas Américas, definir a estrutura do programa e identificar estratégias de implementação atualizadas para melhorar a cobertura vacinal depois da pandemia de COVID-19. Métodos. Um grupo de especialistas em pediatria, epidemiologia, vacinas e saúde pública e global discutiu a situação atual do calendário de vacinação infantil nas Américas, descrevendo a estrutura dos programas e identificando novas estratégias de implementação que poderiam melhorar a cobertura vacinal no contexto pós-pandemia, na sequência dos desafios impostos pela COVID-19 durante mais de dois anos. Resultados. Atualmente, as Américas enfrentam um grande risco de ressurgimento de doenças já controla- das ou eliminadas. Desse modo, é importante identificar novas estratégias para conscientizar os cidadãos sobre os riscos decorrentes da queda das taxas de vacinação, sobretudo em crianças. Conclusões. É necessário adotar novas estratégias, aliadas a uma forte mobilização da população e pro- moção da causa pelos cidadãos, a fim de impedir que os grupos antivacinas fortaleçam sua presença na região e coloquem em risco a credibilidade do Programa Ampliado de Imunização.

Half dose ChAdOx1 nCoV-19 vaccine was equivalent to full doses to reduce moderate and severe COVID-19 cases.

Objectives: Previously, we presented the effectiveness of ChAdOx1 nCoV-19 half-dose (HD) immunization for preventing new COVID-19 cases. Here, we evaluated the administration of an HD of ChAdOx1 nCoV-19 in the primary immunization protocol (up to two doses) in reducing moderate and severe cases, hospitalizations, and deaths when compared to the administration of full doses (FD) after a long-term follow-up. Methods: We evaluated data from 29,469 participants between January 2021 and November 2022 who received an HD or FD vaccine and crossed this information with their medical records to identify those who developed moderate or severe cases. All participants were classified into four groups according to their immunization status and followed 500 days after the last vaccine administration. Results: The propensity-score matching analysis indicates that the administration of the two HDs of ChAdOx1 nCoV-19 was equivalent to the use of two FDs to reduce moderate and severe COVID-19 cases. The relative risk of being infected and developing moderate or severe conditions after the administration of at least one HD or FD was similar 150 or 500 days after the administration of the immunizers. Conclusion: Administering two HDs can be used safely as a cost-effective alternative to the primary immunization protocol.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose.

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4-6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

National Vaccine Coverage Survey 2020: methods and operational aspects.

OBJECTIVE: The national vaccination coverage survey on full vaccination at 12 and 24 months of age was carried out to investigate drops in coverage as of 2016. METHODS: A sample of 37,836 live births from the 2017 or 2018 cohorts living in capital cities, the Federal District, and 12 inner cities with 100 thousand inhabitants were followed for the first 24 months through vaccine record cards. Census tracts stratified according to socioeconomic levels had the same number of children included in each stratum. Coverage for each vaccine, full vaccination at 12 and 24 months and number of doses administered, valid and timely, were calculated. Family, maternal and child factors associated with coverage were surveyed. The reasons for not vaccinating analyzed were: medical contraindications, access difficulties, problems with the program, and vaccine hesitancy. RESULTS: Preliminary results showed that less than 1% of children were not vaccinated, full coverage was less than 75% at all capitals and the Federal District, vaccines requiring more than one dose progressively lost coverage, and there were inequalities among socioeconomic strata, favorable to the highest level in some cities and to the lowest in others. CONCLUSION: There was an actual reduction in full vaccination in all capitals and the Federal District for children born in 2017 and 2018, showing a deteriorating implementation of the National Immunization Program from 2017 to 2019. The survey did not measure the impacts of the COVID-19 pandemic, which may have further reduced vaccination coverage.

The effectiveness of COVID-19 vaccines in Latin America, 2021: a multicenter regional case-control study.

Background: As of September 2022, nearly 1.3 billion doses of COVID-19 vaccine products have been administered in Latin America and the Caribbean, where 27% of global COVID-19 deaths have occurred. This study aimed to estimate the effectiveness of COVID-19 vaccines against lab-confirmed COVID-19 related hospitalizations and deaths among adults in Argentina, Brazil, Chile, and Colombia. Methods: Using a test-negative case control design, we evaluated the effectiveness of a primary vaccination series considering six COVID-19 vaccine products (Sputnik V, mRNA-1273, CoronaVac, ChAdOx1, BNT162b2, Ad26.COV2.S) against lab-confirmed COVID-19 hospitalizations and deaths among 83,708 hospitalized adults from February-December, 2021. Data from hospitalization records, COVID surveillance, and vaccination registries were used. Vaccine effectiveness was estimated using logistic regression ((1-OR) x 100). Findings: The average age of participants was 56.7 (SD = 17.5), and 45,894 (54.8%) were male. Adjusted VE (aVE) estimates for full vaccination against hospitalization were 82% for mRNA-1273 (95% confidence interval (CI) = -30 to 98%), 76% (71%-81%) for BNT162b2, 65% (61-68%) for ChAdOx1, 57% (10-79%) for Sputnik V, 53% (50-56%) for CoronaVac, and 46% (23-62%) for Ad26.COV2.S. Estimates, particularly for CoronaVac, varied by variant. Decreasing aVE was estimated as age increased, particularly for CoronaVac and ChAdOx1. aVE estimates against death were generally higher, with 100% (CI not estimated) for mRNA-1273, 82% (69-90%) for BNT162b2, 73% (69-77%) for ChAdOx1, 65% (60-67%) for CoronaVac, 38% (-75 to 78%) for Sputnik V, 6% (-58 to 44%) for Ad26.COV2.S. Interpretation: Primary series vaccination with available COVID-19 vaccine products was effective against COVID-19 hospitalization and mortality. Effectiveness varied by product and declined with increasing age. Funding: This study was funded by the Pan-American Health Organization (PAHO, World Health Organization (WHO)). PAHO convened and led the study implementation.

Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review

Abstract Objective: To evaluate the behavior of VCR and VCH, per municipality and per vaccines offered at the NVC, to identify priority areas for intervention. Methods: Descriptive study of a time series, using secondary data and accompanied by a narrative review of the literature evaluating VCR and VCH. Vaccines offered to children under one year and to those aged one year in the pre-pandemic period of COVID-19 (2015 to 2019) were selected and compared to those offered during the pandemic period (2020 and 2021 ). Results and discussions: The decrease in VCR and VCH is a process that precedes the COVID-19 pandemic but was intensified during this period. In 2021, the VCR was around 70% for most vaccines. This phenomenon encompasses the entire country; however, it is more intense in the states/municipalities located in the north and northeast regions, suggesting greater difficulty in accessing health services. Conclusion: Low and heterogeneous VCR requires the adoption of practices that were previously implemented, establishing partnerships with governmental and non-governmental institutions, with adequate communication, active search for non-compliance and non-adherence to the regular vaccination program, adopting intra- and extramural vaccination strategies, to reverse the current situation and reduce the risk of recurrence of diseases that have been already controlled and eliminated.

Vaccination coverage in children in the period before and during the COVID-19 pandemic in Brazil: a time series analysis and literature review.

OBJECTIVE: To evaluate the behavior of VCR and VCH, per municipality and per vaccines offered at the NVC, to identify priority areas for intervention. METHODS: Descriptive study of a time series, using secondary data and accompanied by a narrative review of the literature evaluating VCR and VCH. Vaccines offered to children under one year and to those aged one year in the pre-pandemic period of COVID-19 (2015 to 2019) were selected and compared to those offered during the pandemic period (2020 and 2021). RESULTS AND DISCUSSIONS: The decrease in VCR and VCH is a process that precedes the COVID-19 pandemic but was intensified during this period. In 2021, the VCR was around 70% for most vaccines. This phenomenon encompasses the entire country; however, it is more intense in the states/municipalities located in the north and northeast regions, suggesting greater difficulty in accessing health services. CONCLUSIONS: Low and heterogeneous VCR requires the adoption of practices that were previously implemented, establishing partnerships with governmental and non-governmental institutions, with adequate communication, active search for non-compliance and non-adherence to the regular vaccination program, adopting intra- and extramural vaccination strategies, to reverse the current situation and reduce the risk of recurrence of diseases that have been already controlled and eliminated.

Effectiveness, safety, and immunogenicity of half dose ChAdOx1 nCoV-19 COVID-19 Vaccine: Viana project.

Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

[Changes in the pattern of COVID-19 hospitalizations and deaths after substantial vaccination of the elderly in Manaus, Amazonas State, Brazil]. / Mudanças no padrão de internações e óbitos por COVID-19 após substancial vacinação de idosos em Manaus, Amazonas, Brasil.

The impact of COVID-19 vaccination in the elderly has received relatively little attention, particularly in a scenario predominated by the gamma variant. The aim of this study was to assess vaccination coverage and its relationship to changes in the pattern of COVID-19 hospitalizations and deaths in the elderly in Manaus, Amazonas State, Brazil. This was an ecological study with Brazilian Ministry of Health data on hospitalizations and deaths, assessing vaccination coverage based on a two-dose regimen, in addition to two vaccination regimens associated with a significant protective effect, one partial (35 days or more after the first dose of the Oxford/AstraZeneca vaccine) and the other complete (14 days or more after the second dose of the Sinovac-CoronaVac vaccine). Based on the date of initial symptoms, patterns of COVID-19 hospitalizations and deaths were assessed comparatively in elderly 60-69 years and 70 years or more in two groups of Epidemiological Weeks (EW) in 2020 (unvaccinated) and 2021 (vaccinated). Hospitalization and death rates were estimated with Poisson regression. In the groups 60-69 and 70 years or more, vaccination coverage rates were 41.8% and 54.8%, as well as 53.5% and 90.1%, in the EW groups 18-20/2021 and 21-23/2021, respectively. Both EW groups in 2021 showed a substantial change in the patterns of COVID-19 hospitalizations and deaths, with an increase in the risk of hospitalization and death in unvaccinated younger individuals and an important reduction in vaccinated elderly, especially those 60-69 years of age, besides overall reductions of 62% (95%CI: 52-69) and 63% (95%CI: 43-75) in hospitalization and death rates, respectively. Our results emphasize the importance of mass vaccination, especially during an epidemic such as in Manaus, marked by high circulation of the gamma variant.

A avaliação do impacto da vacinação contra a COVID-19 em idosos é escassa, sobretudo em um cenário com predomínio da variante Gama. O objetivo deste estudo foi avaliar a cobertura vacinal e sua relação com mudanças no padrão de internações e óbitos por COVID-19 em idosos de Manaus, Amazonas, Brasil. Este é um estudo ecológico com dados de internações e óbitos do Ministério da Saúde que avaliou a cobertura vacinal, mediante esquema com duas doses, além de dois regimes de vacinação associados a significativo efeito protetor, um parcial (35 ou mais dias após a primeira dose da vacina Oxford/AstraZeneca) e outro completo (14 dias ou mais após a segunda dose da vacina Sinovac-CoronaVac). A partir da data dos primeiros sintomas, padrões de internação e óbito por COVID-19 foram avaliados, comparativamente, em idosos de 60-69 e de 70 anos ou mais, em dois grupos de Semanas Epidemiológicas (SE) de 2020 (não vacinados) e 2021 (vacinados). Taxas de internação e óbito foram estimadas pelo modelo Poisson. Entre 60-69 anos e naqueles com 70 anos ou mais, a cobertura por vacina foi 41,8% e 54,8%, bem como 53,5% e 90,1% nos grupos de SE 18-20/2021 e 21-23/2021, respectivamente. Em ambos os grupos de SE de 2021, observou-se substancial mudança nos padrões de internações e óbitos por COVID-19, com aumento no risco de internação e óbito nos mais jovens não vacinados, e importante redução no número de idosos vacinados, sobretudo naqueles com 60-69 anos, além de redução global de 62% (IC95%: 52-69) e 63% (IC95%: 43-75) nas taxas de internação e óbitos, respectivamente. Nossos resultados reforçam a importância da vacinação em massa, especialmente em contexto epidêmico como o de Manaus, marcado por elevada circulação da variante Gama.

La evaluación del impacto de la vacunación contra la COVID-19 en ancianos es escasa, sobre todo en un escenario con predominio de la variante Gamma. El objetivo de este estudio fue evaluar la cobertura de vacunación y su relación con cambios en el patrón de internamientos y óbitos por COVID-19 en ancianos de Manaos, Amazonas, Brasil. Este es un estudio ecológico con datos de internamientos y óbitos del Ministerio de Salud, que evaluó la cobertura de vacunación, mediante un esquema con dos dosis, además de dos regímenes de vacunación, asociados a un significativo efecto protector, uno parcial (35 o más días tras la primera dosis de la vacuna Oxford/AstraZeneca) y otro completo (14 días o más tras la segunda dosis de la vacuna Sinovac-CoronaVac). A partir de los datos de los primeros síntomas, se evaluaron patrones de internamiento y óbito por COVID-19, comparativamente, en ancianos de 60-69 y de 70 años o más, en dos grupos de Semanas Epidemiológicas (SE) de 2020 (no vacunados) y 2021 (vacunados). Se estimaron tasas de internamiento y óbito mediante el modelo Poisson. Entre 60-69 años y en aquellos con 70 años o más, la cobertura por vacuna fue 41,8% y 54,8%, así como 53,5% y 90,1% en los grupos de SE 18-20/2021 y 21-23/2021, respectivamente. En ambos grupos de SE de 2021, se observó un cambio sustancial en los patrones de internamiento y óbitos por COVID-19, con un aumento en el riesgo de internamiento y óbito en los más jóvenes no vacunados e importante reducción en los ancianos vacunados, sobre todo en aquellos con 60-69 años, además de una reducción global de 62% (IC95%: 52-69) y 63% (IC95%: 43-75) en las tasas de internamiento y óbitos, respectivamente. Nuestros resultados refuerzan la importancia de la vacunación en masa, especialmente en un contexto epidémico como el de Manaos, marcado por una elevada circulación de la variante Gamma.

The SARS-CoV-2 vaccination campaign in Brazil and the invisibility of science evidences. / A campanha de vacinação contra o SARS-CoV-2 no Brasil e a invisibilidade das evidências científicas.

This paper reflects on the vaccination campaign against COVID-19 in Brazil in light of the consideration of scientific evidence in the decision-making process. Brazil has one of the largest and most complete vaccination programs in the world, the National Immunization Program (Programa Nacional de Imunizações or PNI). Unfortunately, in the current context, with the political interference of the federal government, the PNI lost its role in conducting the vaccination campaign against COVID-19. Despite being a vaccination campaign with a lot of potential and one of the most accepted by the population among countries in the world, it presented many problems and left several gaps in the Brazilian scenario. In this sense, it is essential that the quality scientific evidence produced during this period can guide a constant remodeling of the vaccination strategy. Four points deserve to be highlighted: 1) the interval between doses; 2) the interchangeability between vaccines; 3) vaccination in children and adolescentes; and 4) the need for better evidence to define the vaccination strategy in certain groups and age groups.

O presente texto trata de refletir sobre a campanha de vacinação contra COVID-19 no Brasil à luz da consideração das evidências científicas no processo de tomada de decisão. O Brasil possui um dos maiores e mais completos programas de vacinação do mundo, o Programa Nacional de Imunizações (PNI). Infelizmente, no contexto atual, com as interferências políticas do governo federal, o PNI perdeu seu protagonismo na condução da campanha de vacinação contra a COVID-19. Apesar de ser uma campanha de vacinação com muito potencial e uma das mais aceitas pela população entre os países no mundo, apresentou muitos problemas e deixou diversas lacunas no cenário brasileiro. Nesse sentido, é fundamental que as evidências científicas de qualidade produzidas nesse período possam guiar uma remodelagem constante da estratégia de vacinação. Quatro pontos merecem ser destacados: 1) o intervalo entre as doses; 2) a intercambialidade entre vacinas; 3) a vacinação em adolescentes; e 4) a necessidade de melhores evidências para definir a estratégia de vacinação em certos grupos e faixas etárias.

A campanha de vacinação contra o SARS-CoV-2 no Brasil e a invisibilidade das evidências científicas / The SARS-CoV-2 vaccination campaign in Brazil and the invisibility of science evidences

Resumo O presente texto trata de refletir sobre a campanha de vacinação contra COVID-19 no Brasil à luz da consideração das evidências científicas no processo de tomada de decisão. O Brasil possui um dos maiores e mais completos programas de vacinação do mundo, o Programa Nacional de Imunizações (PNI). Infelizmente, no contexto atual, com as interferências políticas do governo federal, o PNI perdeu seu protagonismo na condução da campanha de vacinação contra a COVID-19. Apesar de ser uma campanha de vacinação com muito potencial e uma das mais aceitas pela população entre os países no mundo, apresentou muitos problemas e deixou diversas lacunas no cenário brasileiro. Nesse sentido, é fundamental que as evidências científicas de qualidade produzidas nesse período possam guiar uma remodelagem constante da estratégia de vacinação. Quatro pontos merecem ser destacados: 1) o intervalo entre as doses; 2) a intercambialidade entre vacinas; 3) a vacinação em adolescentes; e 4) a necessidade de melhores evidências para definir a estratégia de vacinação em certos grupos e faixas etárias.

Abstract This paper reflects on the vaccination campaign against COVID-19 in Brazil in light of the consideration of scientific evidence in the decision-making process. Brazil has one of the largest and most complete vaccination programs in the world, the National Immunization Program (Programa Nacional de Imunizações or PNI). Unfortunately, in the current context, with the political interference of the federal government, the PNI lost its role in conducting the vaccination campaign against COVID-19. Despite being a vaccination campaign with a lot of potential and one of the most accepted by the population among countries in the world, it presented many problems and left several gaps in the Brazilian scenario. In this sense, it is essential that the quality scientific evidence produced during this period can guide a constant remodeling of the vaccination strategy. Four points deserve to be highlighted: 1) the interval between doses; 2) the interchangeability between vaccines; 3) vaccination in children and adolescentes; and 4) the need for better evidence to define the vaccination strategy in certain groups and age groups.

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.

Mudanças no padrão de internações e óbitos por COVID-19 após substancial vacinação de idosos em Manaus, Amazonas, Brasil / Changes in the pattern of COVID-19 hospitalizations and deaths after substantial vaccination of the elderly in Manaus, Amazonas State, Brazil / Cambios en el patrón de internamientos y óbitos por COVID-19 tras una elevada vacunación de ancianos en Manaos, Amazonas, Brasil

A avaliação do impacto da vacinação contra a COVID-19 em idosos é escassa, sobretudo em um cenário com predomínio da variante Gama. O objetivo deste estudo foi avaliar a cobertura vacinal e sua relação com mudanças no padrão de internações e óbitos por COVID-19 em idosos de Manaus, Amazonas, Brasil. Este é um estudo ecológico com dados de internações e óbitos do Ministério da Saúde que avaliou a cobertura vacinal, mediante esquema com duas doses, além de dois regimes de vacinação associados a significativo efeito protetor, um parcial (35 ou mais dias após a primeira dose da vacina Oxford/AstraZeneca) e outro completo (14 dias ou mais após a segunda dose da vacina Sinovac-CoronaVac). A partir da data dos primeiros sintomas, padrões de internação e óbito por COVID-19 foram avaliados, comparativamente, em idosos de 60-69 e de 70 anos ou mais, em dois grupos de Semanas Epidemiológicas (SE) de 2020 (não vacinados) e 2021 (vacinados). Taxas de internação e óbito foram estimadas pelo modelo Poisson. Entre 60-69 anos e naqueles com 70 anos ou mais, a cobertura por vacina foi 41,8% e 54,8%, bem como 53,5% e 90,1% nos grupos de SE 18-20/2021 e 21-23/2021, respectivamente. Em ambos os grupos de SE de 2021, observou-se substancial mudança nos padrões de internações e óbitos por COVID-19, com aumento no risco de internação e óbito nos mais jovens não vacinados, e importante redução no número de idosos vacinados, sobretudo naqueles com 60-69 anos, além de redução global de 62% (IC95%: 52-69) e 63% (IC95%: 43-75) nas taxas de internação e óbitos, respectivamente. Nossos resultados reforçam a importância da vacinação em massa, especialmente em contexto epidêmico como o de Manaus, marcado por elevada circulação da variante Gama.

The impact of COVID-19 vaccination in the elderly has received relatively little attention, particularly in a scenario predominated by the gamma variant. The aim of this study was to assess vaccination coverage and its relationship to changes in the pattern of COVID-19 hospitalizations and deaths in the elderly in Manaus, Amazonas State, Brazil. This was an ecological study with Brazilian Ministry of Health data on hospitalizations and deaths, assessing vaccination coverage based on a two-dose regimen, in addition to two vaccination regimens associated with a significant protective effect, one partial (35 days or more after the first dose of the Oxford/AstraZeneca vaccine) and the other complete (14 days or more after the second dose of the Sinovac-CoronaVac vaccine). Based on the date of initial symptoms, patterns of COVID-19 hospitalizations and deaths were assessed comparatively in elderly 60-69 years and 70 years or more in two groups of Epidemiological Weeks (EW) in 2020 (unvaccinated) and 2021 (vaccinated). Hospitalization and death rates were estimated with Poisson regression. In the groups 60-69 and 70 years or more, vaccination coverage rates were 41.8% and 54.8%, as well as 53.5% and 90.1%, in the EW groups 18-20/2021 and 21-23/2021, respectively. Both EW groups in 2021 showed a substantial change in the patterns of COVID-19 hospitalizations and deaths, with an increase in the risk of hospitalization and death in unvaccinated younger individuals and an important reduction in vaccinated elderly, especially those 60-69 years of age, besides overall reductions of 62% (95%CI: 52-69) and 63% (95%CI: 43-75) in hospitalization and death rates, respectively. Our results emphasize the importance of mass vaccination, especially during an epidemic such as in Manaus, marked by high circulation of the gamma variant.

La evaluación del impacto de la vacunación contra la COVID-19 en ancianos es escasa, sobre todo en un escenario con predominio de la variante Gamma. El objetivo de este estudio fue evaluar la cobertura de vacunación y su relación con cambios en el patrón de internamientos y óbitos por COVID-19 en ancianos de Manaos, Amazonas, Brasil. Este es un estudio ecológico con datos de internamientos y óbitos del Ministerio de Salud, que evaluó la cobertura de vacunación, mediante un esquema con dos dosis, además de dos regímenes de vacunación, asociados a un significativo efecto protector, uno parcial (35 o más días tras la primera dosis de la vacuna Oxford/AstraZeneca) y otro completo (14 días o más tras la segunda dosis de la vacuna Sinovac-CoronaVac). A partir de los datos de los primeros síntomas, se evaluaron patrones de internamiento y óbito por COVID-19, comparativamente, en ancianos de 60-69 y de 70 años o más, en dos grupos de Semanas Epidemiológicas (SE) de 2020 (no vacunados) y 2021 (vacunados). Se estimaron tasas de internamiento y óbito mediante el modelo Poisson. Entre 60-69 años y en aquellos con 70 años o más, la cobertura por vacuna fue 41,8% y 54,8%, así como 53,5% y 90,1% en los grupos de SE 18-20/2021 y 21-23/2021, respectivamente. En ambos grupos de SE de 2021, se observó un cambio sustancial en los patrones de internamiento y óbitos por COVID-19, con un aumento en el riesgo de internamiento y óbito en los más jóvenes no vacunados e importante reducción en los ancianos vacunados, sobre todo en aquellos con 60-69 años, además de una reducción global de 62% (IC95%: 52-69) y 63% (IC95%: 43-75) en las tasas de internamiento y óbitos, respectivamente. Nuestros resultados refuerzan la importancia de la vacunación en masa, especialmente en un contexto epidémico como el de Manaos, marcado por una elevada circulación de la variante Gamma.

Behavioral factors associated with multiple-type HPV genital infections: data from a cross-sectional study in young women in Brazil.

OBJECTIVES: To investigate the pattern of multiple human papillomavirus (HPV) infections and associated factors in young women who access the Brazilian public health care system to better understand the characteristics of multiple HPV infections, a critical issue in this era of multivalent vaccines. METHODS: This was a cross-sectional, multicenter study with sexually active unvaccinated women (16-25 years old) from 119 primary Brazilian healthcare centers between September 2016 and November 2017. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. RESULTS: Of the 5268 women, 33.00% (95% CI 31.07-34.92) had multiple infections. At least one type of high-risk HPV was present in 85.50% of all multiple infections. All HPV types were detected more frequently in association with other types than alone. Young individuals who were single or in a casual relationship and those who had more than one sexual partner in the past year were more likely to have multiple infections. CONCLUSIONS: In this work, a high rate of multiple HPV infections among unvaccinated young adults tended to increase due to certain risk factors. Such data can provide insight for decision makers in the development of public policies regarding HPV prevention.

Understanding the characteristics of multiple infections is critical in the era of HPV multivalent vaccines for the prevention of cervical carcinomas. Therefore, in this cross-sectional study, we aimed to investigate the pattern of multiple HPV infections and associated factors in 5,268 sexually active unvaccinated women (16­25 years old) who access the Brazilian public health care system. Cervical samples were collected by trained health professionals, and HPV detection was performed in a central laboratory by Linear Array. A total of 33.00% (95% CI 31.07­34.92) had multiple infections (60.43% of the HPV-positive sample). The number of HPV types in a multiple infection ranged from 2 to 14 different types. The viral types more frequently identified were HPV 16 and 52. All HPV types were detected more frequently in association with other types than alone. The incidence of multiple infections was 1.29 times higher in single than in married or cohabitating participants. Women who had two or more partners in the last year also had higher rates of multiple infections than those who had fewer than two sexual partners. In conclusion, a high prevalence of multiple infections prior to the national HPV immunization program was observed, especially with the increase in less safe behavior factors.

Effects of the COVID-19 pandemic on routine pediatric vaccination in Brazil.

BACKGROUND: COVID-19 pandemic has disrupted health services, including vaccination demand. We describe the impact of the COVID-19 pandemic on routine pediatric vaccination in Brazil. METHODS: We conducted a retrospective analysis of all vaccine doses provided to children aged 0-6 years from January 2019 to December 2020. We obtained data stratified by age group (0 to 2 years and >2 to 6 years) and Brazilian region. Difference-in-difference (DiD) analyses were performed to compare vaccine uptake in the pre-pandemic (January-February), stay-at-home (March-June), and reopening (July-December) periods. RESULTS: The number of vaccine doses administered declined in the stay-at-home period. For children aged 0 to 2 years, the highest reductions were recorded in the North (-25.3%), Northeast (-16.8%) and Central-West (-10.2%) regions. For children aged >2 to 6 years, the highest decline was observed in the North (DiD = -27.2%) and South (DiD = -14.0%) regions. The number of vaccine doses administered in the reopening period has slightly increased in all regions. CONCLUSIONS: Vaccination decreased during the COVID-19 pandemic. Although the number of doses recovered in part during the reopening phase, additional strategies, such as increased public awareness and vaccination booster campaigns are required.

Analyzing the importance of attributes for Brazilian consumers to replace conventional beef with cultured meat.

Cultured meat has been proposed as an alternative source of protein to overcome the environmental and ethical problems associated with conventional meat production. However, the lack of consumers' acceptance could be a major barrier to the introduction of cultured meat on a large scale. Despite Brazil being one of the countries that consumes the most meat per capita, little is known about Brazilian consumers' preferences for alternative meat. The objective of this study is to identify which attributes influence consumers to possibly replace conventional beef meat with cultured meat in Brazil. An online survey was conducted, and Best-worst scaling methodology was applied to a sample of 225 consumers. The sampling leaned towards educated and employed residents of the southeast region of Brazil, which might not fully represent the Brazilian population. Despite limitations in terms of the sampling demographic, overall, Brazilians appear to be willing to consume cultured meat: 80.9% of the sample would be willing to try it, 61.3% would be willing to eat it regularly, and 56.9% would be willing to eat cultured meat as a replacement for conventionally produced beef. Despite the focus of this study being on attributes of a hypothetical product that is not commercially available, which might pose difficulty to consumers to predict their future consumption behavior, results show that the most important attributes influencing consumers to possibly replace conventional beef meat by cultured meat in Brazil are anticipated risk of zoonotic diseases, anticipated healthiness and anticipated food safety conditions. Attributes related to benefits at a global societal level and intrinsic characteristics of cultured meat were less important.

Evaluation of the National Immunization Program Surveillance System - Vaccination Record Module, Brazil, 2017. / Avaliação do Sistema de Vigilância do Programa Nacional de Imunizações - Módulo Registro do Vacinado, Brasil, 2017.

OBJETIVO: To evaluate the National Immunization Program Immunization Surveillance System, based on its Vaccination Record module, for Brazil in 2017. METHODS: This was a descriptive study using the Guidelines for Evaluating Public Health Surveillance Systems, published by the Centers for Disease Control and Prevention (CDC/Atlanta/GA/United States) to evaluate the attributes of simplicity, flexibility, data quality, sensitivity, timeliness and usefulness of the system for six vaccines on the child immunization schedule. RESULTS: The Immunization Surveillance System was considered complex in its description; flexible to changes in the immunization schedule; of poor data quality for the DTP and rotavirus vaccines; regular acceptability; high sensitivity for the BCG vaccine; untimely for the hepatitis B vaccine and useful for the purposes of the National Immunization Program. CONCLUSION: The data quality, acceptability and timeliness results were not satisfactory, so that actions are needed to enhance the information system.