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.

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.

Estratégia do Ministério da Saúde do Brasil para aumento das coberturas vacinais nas fronteiras / Brazilian Ministry of Health strategy to increase vaccination coverage at borders / Estrategia del Ministerio de Salud de Brasil para aumentar las tasas de cobertura de vacunación en las fronteras

[RESUMO]. Objetivo. Avaliar a implementação de estratégia do “Plano de Ação: Estratégia de Vacinação nas Fronteiras – Agenda 2022” do Ministério da Saúde nas 33 cidades gêmeas e avaliar o incremento das coberturas vacinais (CV) brasileiras. Métodos. Ensaio clínico comunitário, do tipo antes e depois. Analisou-se a realização da estratégia, bem como comparadas as CV pré e pós-intervenção em dois tempos: P1 (pré-intervenção) e P2 (pós-intervenção). Análises estatísticas sobre a CV, no P1 e P2, foram calculados os valores de média entres os municípios, desvio padrão e diferença entre as coberturas dos dois períodos. Resultados. Observou-se integração entre as equipes de Atenção Primária à Saúde (APS), Vigilância, Imunização e Distrito Sanitário Especial Indígena (DSEI), porém com dificuldades, como aquelas inerentes ao fluxo migratório. Ressalta-se que o fluxo imigratório é um dos desafios no contexto da imunização, APS e DSEI, entretanto, a esta dificuldade soma-se a polarização entre os serviços (imunização, APS e DISEI), ocasionando um desafio para a integração dos setores. Em relação à análise das CV, após a realização das oficinas, foram totalizadas 50 977 doses aplicadas na população geral nas 33 cidades-gêmeas do Brasil. Houve incremento das coberturas vacinais de crianças de até um ano de idade nos locais avaliados após a intervenção, o que pode ser importante para aumentar as CV no Brasil. Conclusão. Houve incremento das coberturas vacinais das crianças até um ano de idade nos locais avalia- dos após a intervenção e isso influenciou no aumento das CV no Brasil.

[ABSTRACT]. Objective. Evaluate the implementation of the Ministry of Health’s “Action Plan: Border Vaccination Strategy – Agenda 2022” in the Brazil’s 33 twin cities and evaluate the increase in the country’s vaccination coverage (VC). Methodology. Pre-post community clinical trial. Implementation of the strategy was analyzed, and pre- and post-intervention VC were compared in two stages: P1 (pre-intervention) and P2 (post-intervention). Based on statistical analyses of P1 and P2 coverage, calculations were made of municipal averages, standard deviation, and difference in VC between the two periods. Results. Integration was observed between the primary health care (PHC), surveillance, immunization, and special indigenous health district (DSEI) teams, although there were difficulties, for example, in relation to migratory flows. While immigration flows present challenges in the areas of immunization, PHC, and DSEI, the difficulties are compounded by the polarization of these services, which hinders intersectoral integration. After carrying out the workshops, a total of 50 977 doses were administered in the general population in the 33 twin cities. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, which may be relevant in terms of increasing VC in Brazil. Conclusion. There was an increase in vaccination coverage in children up to 1 year of age in the locations evaluated after the intervention, helping to increase VC in Brazil.

[RESUMEN]. Objetivo. Evaluar la aplicación de la Estrategia de Vacunación en las Fronteras - Agenda 2022, que forma parte del Plan de Acción del Ministerio de Salud en las 33 ciudades hermanas y evaluar el aumento de las tasas de cobertura de vacunación en Brasil. Métodos. Ensayo clínico comunitario realizado antes y después de la intervención correspondiente. Se analizó la aplicación de la estrategia y se compararon las tasas de cobertura de vacunación antes y después de la intervención en dos periodos: P1 (pre-intervención) y P2 (post-intervención). En los análisis estadísticos de la tasa de cobertura de vacunación en P1 y P2 se calcularon los valores de media y desviación estándar de los municipios y la diferencia entre las tasas de cobertura de los dos periodos. Resultados. Se observó una integración entre los equipos de Atención Primaria de Salud, Vigilancia, Inmu- nización y el Distrito Especial de Salud Indígena (DISEI), pero con dificultades, como las inherentes al flujo migratorio. Cabe destacar que el flujo migratorio es uno de los desafíos en el contexto de la inmunización, la atención primaria de salud y el DISEI, dificultad que se ve agravada por la polarización entre los servicios (inmunización, atención primaria de salud y el DISEI), lo que supone un reto para la integración de los sectores. Por lo que respecta al análisis de las tasas de cobertura de vacunación llevado a cabo después de realizar los talleres, se administró un total de 50 977 dosis a la población general en las 33 ciudades hermanas de Brasil. Hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados después de la intervención, lo que puede ser importante para aumentar las tasas de cobertura de Brasil. Conclusión. Después de la intervención hubo un aumento de las tasas de cobertura de vacunación de menores de hasta un año de edad en los lugares evaluados, lo cual influyó en el incremento de las tasas de cobertura de Brasil.

Restoring High Vaccine Coverage in Brazil: Successes and Challenges

Facing the decline in vaccine coverage observed since 2016, the new Brazilian government committed to reversing this scenario. To achieve this, the Federal Government launched the National Vaccination Movement and the 'Health with Science' platform to combat vaccine misinformation, promoted Microplanning, providing tools for decision-making at the territorial level, allocated 30 million dollars to states and municipalities to implement innovative vaccination strategies, standardized the rules of the information systems for the registration of vaccine doses, and directed data to the National Health Data Network (RNDS). Reversing the declining trend of vaccination coverage in Brazil is challenging, but within just one year, it is possible to observe significant results from governmental actions. Out of the eight recommended vaccines by the age of one, seven showed an increase in vaccination coverage in 2023 compared to 2022: Most states showed improvements in vaccination coverage. Many challenges persist in advancing the vaccination agenda. However, there are reasons to celebrate the reversal of the declining trend in coverage of several vaccines in this first year of government and the increase in the number of municipalities that have fully achieved the vaccination coverage target. The National Vaccination Movement, with public opinion awareness, the resumption of regionalized communication campaigns, localized micro-planning actions including extramural vaccination strategies, and the integration of information systems, has been decisive in strengthening work in the territories and thus restoring a culture of immunization, a source of pride in the country and internationally recognized, throughout the 50 years of the National Immunization Program

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation.

The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Yellow Fever Vaccine-Associated Viscerotropic Disease among Siblings, São Paulo State, Brazil.

We describe 5 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) in 2 familial clusters during the 2017-2018 yellow fever (YF) vaccination campaign in São Paulo state, Brazil. The first case was that of a 40-year-old white man who died of icterohemorrhagic syndrome, which was confirmed to be YEL-AVD by using real-time reverse transcription PCR to detect 17DD YF vaccine in the liver. Ten years previously, his brother died of a clinically similar disease without a confirmed diagnosis 9 days after YF vaccination. The second cluster included 3 of 9 siblings in whom hepatitis developed in the first week after receiving fractionated doses of YF vaccine. Two of them died of hemorrhagic diathesis and renal and respiratory failure, and 17DD-YF vaccine was detected in serum samples from all patients and in the liver in 1 case. Genetic factors might play a substantial role in the incidence of YEL-AVD.

Measles, mumps and rubella vaccine 12 months after hematopoietic stem cell transplantation

ABSTRACT The measles, mumps and rubella (MMR) vaccine is usually recommended from 24 months after a hematopoietic stem cell transplant (HSCT). Some authors have demonstrated that the MMR vaccination can be safe from 12 months post-HSCT in non-immunosuppressed patients, as recommended by the Brazilian National Immunization Program/Ministry of Health, since 2006. The objectives of this study were to evaluate when patients received MMR vaccine after an HSCT in our care service and if there were reports of any side effects. We retrospectively reviewed the records of HSCT recipients who received at least one MMR dose in our care service, a quaternary teaching hospital in Sao Paulo city, Brazil, from 2017 to 2021. We identified 82 patients: 75.6% (90.1% in the autologous group and 45.1% in the allogeneic group) were vaccinated before 23 months post-transplantation. None reported side effects following the vaccination. Our data support that the MMR vaccination is safe from 12 to 23 months after HSCT.

Hospitalizations for COVID-19 in a tertiary hospital in Brazil: a parallel with vaccination.

This study aimed to evaluate the COVID-19 hospitalizations in a tertiary hospital by age group and month, considering the introduction and the advance of the vaccination against the disease. The laboratory-confirmed COVID-19-associated hospitalizations among people aged 20 years or older, that occurred between March 2020 and June 2021, were distributed by month of symptom onset and age group. The proportion of hospitalizations by age group was calculated for the year 2021. The proportions were compared using the chi-square test for trends. The marks of vaccination advances among different age groups were taken from the official website LocalizaSUS. In 2020, hospitalizations among people aged 60-80 years old were the most frequent (39.1%). From January-June 2021, when the vaccination commenced, while hospitalizations of patients aged 20 to < 40 and 40 to 60 years old showed an increasing trend, the older age groups and those with vaccination recommendations (from 60 to < 80 and from 80 or over) showed a downward trend. As of June 2021, with widespread vaccination, a drop in hospitalizations was observed in > 60 years old. At 20 to <40 and 40 to < 60, an increase in hospitalizations was observed. It demonstrates the important role of vaccination in combating the COVID-19 pandemic.

Impact of polio vaccines (oral polio vaccine - OPV or inactivated polio vaccine - IPV) on rotavirus vaccine-associated intussusception.

Although safe, rotavirus vaccines have been associated with increased intussusception risk. In Brazil, after the oral human rotavirus vaccine (OHRV) introduction in the childhood immunization, in 2006, increased intussusception risk was identified after the second OHRV dose, whereas in other countries, higher risk was associated to the first vaccine dose. It was hypothesized that the concomitant use of oral poliovirus vaccine (OPV) in Brazil might explain this difference. In 2012, the inactivated polio vaccine (IPV) was adopted in the first two doses of Brazilian childhood immunization schedule, creating an opportunity to study the subject. Our objective was analyzing the impact of polio vaccines on rotavirus-associated intussusception. We used surveillance data on intussusception in infants living in São Paulo State. Two periods were considered: an OPV-period (March 2006 to June 2012) and an IPV-period (October 2012 to December 2017). The period from June to September 2012 were considered as transition. Self-controlled case series analysis with event-dependent exposure was performed, considering two risk periods (7 and 21 days post-vaccination). We identified 325 intussusception cases in infants reported to the surveillance systems during the study period. The statistical analysis included 221 cases that occurred within 60 days after vaccination. Overall, a higher intussusception risk was observed in the first week after vaccination for both the first (Relative Incidence [RI] = 4.3, 95%CI 2.8-6.5, p < .001) and second vaccine doses (RI = 4.2, 95%CI 2.7-6.4; p < .001). There were no statistically significant differences in intussusception risk according to the rotavirus vaccine dose and the polio vaccine (OPV or IPV) administered concomitantly.

Hospitalizations for COVID-19 in a tertiary hospital in Brazil: a parallel with vaccination

ABSTRACT This study aimed to evaluate the COVID-19 hospitalizations in a tertiary hospital by age group and month, considering the introduction and the advance of the vaccination against the disease. The laboratory-confirmed COVID-19-associated hospitalizations among people aged 20 years or older, that occurred between March 2020 and June 2021, were distributed by month of symptom onset and age group. The proportion of hospitalizations by age group was calculated for the year 2021. The proportions were compared using the chi-square test for trends. The marks of vaccination advances among different age groups were taken from the official website LocalizaSUS. In 2020, hospitalizations among people aged 60-80 years old were the most frequent (39.1%). From January-June 2021, when the vaccination commenced, while hospitalizations of patients aged 20 to < 40 and 40 to 60 years old showed an increasing trend, the older age groups and those with vaccination recommendations (from 60 to < 80 and from 80 or over) showed a downward trend. As of June 2021, with widespread vaccination, a drop in hospitalizations was observed in > 60 years old. At 20 to <40 and 40 to < 60, an increase in hospitalizations was observed. It demonstrates the important role of vaccination in combating the COVID-19 pandemic.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in inadvertently vaccinated healthy children.

Twenty-seven children aged seven months to 5 years were inadvertently vaccinated with a COVID-19 vaccine, the CoronaVac (Sinovac, China), an inactivated SARS-CoV-2 vaccine, in two different cities of Sao Paulo State, Brazil. After the event, these children were monitored by local pediatricians and serum samples were collected at the first visit and 30 days after vaccination and tested for SARS-CoV-2 S1 serology with Ortho total IgG anti-S1 protein and Cpass, an ACE2 receptor binding domain inhibition assay. Only one child had a mild symptom after vaccination, with no other adverse events documented up to the 30 days follow-up. Of 27 children tested 3-9 days after vaccination, 5 (19%) had positive serology suggesting a previous natural SARS-CoV-2 infection, with all 19 tested on day 30 after vaccination and presenting with positive tests, with an increment of antibody titers in those initially positive. A low Cpass binding inhibition was observed in the first collection in 11 seronegative cases, with high titers among those anti-S1 positive. All children showed an important increase in antibody titers on day 30. The event allowed the documentation of a robust serological response to one dose of CoronaVac in this small population of young children, with no major adverse effects. Although it was an unfortunate accident, this event may contribute with future vaccine strategies in this age group. The data suggest that CoronaVac is safe and immunogenic for children.

CCL3, CCL5, IL-15, IL-1Ra and VEGF compose a reliable algorithm to discriminate classes of adverse events following 17DD-YF primary vaccination according to cause-specific definitions.

In the present study, a range of serum biomarkers were quantified in suspected cases of adverse events following YF immunization (YEL-AEFI) to propose a reliable laboratorial algorithm to discriminate confirmed YEL-AEFI ("A1" class) from cases with other illnesses ("C" class). Our findings demonstrated that increased levels of CXCL8, CCL2, CXCL10, IL-1ß, IL-6 and TNF-α were observed in YEL-AEFI ("A1" and "C" classes) as compared to primary vaccines without YEL-AEFI [PV(day 3-28)] and reference range (RR) controls. Notably, increased levels of CCL3, CCL4, CCL2, CCL5, IL-1ß, IL-15, IL-1Ra and G-CSF were found in "A1" as compared to "C" class. Venn diagrams analysis allowed the pre-selection of biomarkers for further analysis of performance indices. Data demonstrated that CCL3, CCL5, IL-15 and IL-1Ra presented high global accuracy (AUC = 1.00) to discriminate "A1" from "C". Decision tree was proposed with a reliable algorithm to discriminate YEL-AEFI cases according to cause-specific definitions with outstanding overall accuracy (91%). CCL3, CCL5, IL-15 and IL-1Ra appears as root attributes to identify "A1" followed by VEGF as branch nodes to discriminate Wild Type YFV infection ("C(WT-YFV)") from cases with other illnesses ("C*"). Together, these results demonstrated the applicability of serum biomarker measurements as putative parameters towards the establishment of accurate laboratorial tools for complementary differential diagnosis of YEL-AEFI cases.