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.

Zika, dengue and chikungunya population prevalence in Rio de Janeiro city, Brazil, and the importance of seroprevalence studies to estimate the real number of infected individuals.

In the last 40 years, Latin America countries, including Brazil, have suffered from the emergence and reemergence of arboviruses, first Dengue (DENV) and recently Zika (ZIKV) and Chikungunya (CHIKV). All three arboviruses are currently endemic in Brazil and have caused major outbreaks in recent years. Rio de Janeiro city, host of the last Summer Olympic Games and the Football World Cup, has been specially affected by them. A surveillance system based on symptomatic reports is in place in Rio, but the true number of affected individuals is unknown due to the great number of Zika, Dengue and Chikungunya asymptomatic cases. Seroprevalence studies are more suitable to evaluate the real number of cases in a given population. We performed a populational seroprevalence survey in Rio, with recruitment of a sample of volunteers of all ages and gender from July to October 2018, within randomly selected census tracts and household. A total of 2,120 volunteers were interviewed and tested with rapid immunochromatographic test for ZIKV, DENV and CHIKV. Individuals with positive results for IgG and/or IgM from only one virus were classified accordingly, while those with test results positive for both ZIKV and DENV were classified as flaviviruses. We corrected for sample design and non-response in data analysis, and calculated point estimate prevalence and 95% confidence intervals for each virus. Arbovirus prevalence in the Rio's population (n = 6,688,927) was estimated at 48.6% [95% CI 44.8-52.4] (n = 3,254,121) for flaviviruses and at 18.0% [95% CI 14.8-21.2] (n = 1,204,765) for CHIKV. Approximately 17.0% [95% CI 14.1-20.1] (n = 1,145,674) of Rio´s population had no contact with any of the three arboviruses. The reported cases of Zika, Dengue and Chikungunya by the current surveillance system in place is insufficient to estimate their real numbers, and our data indicate that Zika seroprevalence could be at least five times and Chikungunya 45 times bigger. The high number of individuals having never been infected by any of the three arboviruses, may indicate a proper scenario for future outbreaks.

Neurologic manifestations in emerging arboviral diseases in Rio de Janeiro City, Brazil, 2015-2016.

INTRODUCTION: Dengue has affected Rio de Janeiro City since the 1980s. The sequential Zika and chikungunya virus introductions during 2015 aggravated the health scenario, with 97,241 cases of arboviral diseases reported in 2015-2016, some with neurological disorders. METHODS: Arbovirus-related neurologic cases were descriptively analyzed, including neurological syndromes and laboratory results. RESULTS: In total, 112 cases with non-congenital neurologic manifestations (Guillain-Barré syndrome, 64.3%; meningoencephalitis, 24.1%; acute demyelinating encephalomyelitis, 8%) were arbovirus-related; 43.7% were laboratory-confirmed, of which 57.1% were chikungunya-positive. CONCLUSIONS: Emerging arbovirus infections brought opportunities to study atypical, severe manifestations. Surveillance responses optimized case identification and better clinical approaches.

Neurologic manifestations in emerging arboviral diseases in Rio de Janeiro City, Brazil, 2015-2016

Abstract INTRODUCTION Dengue has affected Rio de Janeiro City since the 1980s. The sequential Zika and chikungunya virus introductions during 2015 aggravated the health scenario, with 97,241 cases of arboviral diseases reported in 2015-2016, some with neurological disorders. METHODS Arbovirus-related neurologic cases were descriptively analyzed, including neurological syndromes and laboratory results. RESULTS In total, 112 cases with non-congenital neurologic manifestations (Guillain-Barré syndrome, 64.3%; meningoencephalitis, 24.1%; acute demyelinating encephalomyelitis, 8%) were arbovirus-related; 43.7% were laboratory-confirmed, of which 57.1% were chikungunya-positive. CONCLUSIONS Emerging arbovirus infections brought opportunities to study atypical, severe manifestations. Surveillance responses optimized case identification and better clinical approaches.

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.

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.

Epidemiologia da doença meningocócica na cidade do Rio de Janeiro: modificaçöes após vacinaçäo contra os sorogrupos B e C / Epidemiology of meningococcal disease in the city of Rio de janeio: changes after vaccination against B and C serogroups

A doença meningocócica tem sido um sério problema de saúde pública no município do Rio de Janeiro nos últimos 10 anos, com altas taxas de incidência em crianças de baixa idade, elevada letalidade e predomínio do sorogrupo B. Em dezembro de 1994 foi realizada a segunda campanha de vacinaçäo anti-meningocócica contra os sorogrupos B e C, visando à imunizaçäo de crianças de 6 meses a 13 anos de idade. Foram vacinadas com duas doses cerca de 950 mil crianças. A vacina utilizada foi a produzida pelo Instituto Finlay de Cuba. Em 1995 foi observada uma modificaçäo no comportamento da doença, quando passou a predominar o sorogrupo C e aumentou a incidência global da doença, particularmente entre os menores de 1 ano, adolescentes e adultos jovens. Nos grupos etários vacinados, a incidência foi menor que no ano de 1994, em funçäo da diminuiçäo do sorogrupo B. Näo foram observadas modificaçöes importantes no comportamento da letalidade.