A randomized, double-blind, non-inferiority trial comparing the immunogenicity and safety of two seasonal inactivated influenza vaccines in adults.

BACKGROUND: To enhance the production and availability of influenza vaccines in different regions of the world is paramount to mitigate the global burden of this disease. Instituto Butantan developed and manufactured an embryonated egg-based inactivated split-virion trivalent seasonal influenza vaccine as part of a technology transfer partnership with Sanofi Pasteur. METHODS: This is a phase IV, randomized, double-blind, active-controlled, multicenter clinical trial including adults 18-60 and > 60 years recruited during the 2019 southern hemisphere influenza season. Subjects were randomized 1:1 to receive either the Sanofi Pasteur Trivalent Seasonal Influenza Vaccine (SP-TIV) or Instituto Butantan Trivalent Seasonal Influenza Vaccine (IB-TIV). Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination. RESULTS: 624 participants were randomized and vaccinated. In both intention-to-treat and per-protocol analysis, non-inferiority of the SP-TIV versus IB-TIV was demonstrated for the three influenza strains. In the per-protocol analysis, the SP-GMT/IB-GMT ratios for H1N1, H3N2, and B were 0.9 (95%CI, 0.7-1.1), 1.2 (95%CI, 1.0-1.4), and 1.1 (95%CI, 0.9-1.3), respectively. Across vaccination groups, the most common adverse reactions (AR) were limited to the injection-site, including pain and tenderness. The majority of the ARs were graded 1 and/or 2 and lasted less than one day. No serious adverse reaction was observed. CONCLUSION: This study demonstrated the non-inferiority of the immunogenicity of a single-dose of Instituto Butantan versus a single dose of the Sanofi Pasteur Seasonal Trivalent Influenza Vaccine in adults. Both vaccines were well tolerated and presented similar safety profiles.

Shift in the timing of respiratory syncytial virus circulation in a subtropical megalopolis: implications for immunoprophylaxis.

Respiratory syncytial virus (RSV) is the most common cause of severe respiratory infections worldwide, and an important cause of childhood bronchiolitis, pneumonia, and mortality. Although prevention of RSV infection by immunoprophylaxis with palivizumab has proved effective, a precise understanding of the timing of RSV outbreaks is necessary to ensure that infants are protected when RSV is circulating. In this study a consistent shift in the seasonal patterns of RSV circulation in southeast Brazil (São Paulo) is reported based on the analysis of 15 years of viral surveillance. Surveillance was conducted from 1996 to 2010 and involved the collection of samples from children with symptoms of acute respiratory infection. Putative changes in school terms, in the proportion of RSV genotypes infecting children and in the seasonal dynamics of several climatic parameters during the period were also investigated. The results revealed a progression in the timing of RSV seasons, with a shift in the onset and peak of RSV epidemics from 2007 onwards. Although lower rainfall and temperatures were associated with the onset of outbreaks, there was no evidence of changes in climate, school terms or in the relative proportion of genotypes in the period analyzed. These findings have direct implications for improving the prophylactic use of palivizumab, and stress the importance of fine tuning prophylaxis with recent surveillance data. In the case of São Paulo, palivizumab prophylaxis should be initiated earlier than suggested currently. Similar adjustments may be necessary in other regions.

Dose-sparing effect of two adjuvant formulations with a pandemic influenza A/H7N9 vaccine: A randomized, double-blind, placebo-controlled, phase 1 clinical trial.

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15µg H7N9, 1B) IB160 + 7.5µg H7N9, 1C) IB160 + 3.75µg H7N9, 2A) SE + 15µg H7N9, 2B) SE + 7.5µg H7N9, 2C) SE + 3.75µg H7N9, 3) unadjuvanted vaccine 15µg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.

Immunogenicity and tolerability of a virosome influenza vaccine compared to split influenza vaccine in patients with sickle cell anemia.

The immunogenicity and tolerability of virosome and of split influenza vaccines in patients with sickle cell anemia (SS) were evaluated. Ninety SS patients from 8 to 34 years old were randomly assigned to receive either virosome (n=43) or split vaccine (n=47). Two blood samples were collected, one before and one 4-6 weeks after vaccination. Antibodies against viral strains (2006) A/New Caledonia (H1N1), A/California (H3N2), B/Malaysia were determined using the hemagglutinin inhibition test. Post-vaccine reactions were recorded over 7 days. Seroconversion rates for H1N1, H3N2 and B were 65.1%, 60.4% and 83.7% for virosome vaccine, and 68.0%, 61.7% and 68.0% for split vaccine. Seroprotection rates for H1N1, H3N2 e B were 100%, 97.6% and 69.7% for virosome, and 97.8%, 97.8% and 76.6% for split vaccine. No severe adverse reactions were recorded. Virosome and split vaccines in patients with sickle cell anemia were equally immunogenic, with high seroconversion and seroprotection rates. Both vaccines were well tolerated.

Meningoencefalite fatal por vírus coxsackie B2 em escolar / Coxsackie B2 viirus fatal meningoencephalitis in a student

Objetivo: Apresentar o caso de uma menina previamente hígida, com evolução fatal devido a meningoencefalite por víirus Coxsackie B2. Métodos: Os autores descrevem um caso de uma criança do sexo feminino com, meningoencefalite fatal por vírus Coxsackie B2 e apresentam revisão da literatura (Medline e Licacs). Resultados: É descrito um caso de uma menina de oito anos de idade, que apresentou quadro meningoencefalítico de má evolução, resultando em óbito no 32§ dia de internação. Os exames realizados mostraram sorologia positiva para Coxsackie B2, sendo o vírus isolado de duas amostras de fezes. O exame liquórico mostrou aumento maior que quatro vezes na titulação para Coxsackie B2. Conclusões: A evolução para óbito de pacientes hígidos apresentando encefalite por enterovírus, conforme o descrito, é pouco referido na literatura, talvez por falta de suspeita clínica. O relato deste caso demonstra a importância do diagnóstico etiológico precoce nas meningoencefalites e da busca de tratamento etiológico específico

Investigaçäo etiológica em casos de conjuntivite hemorrágica aguda em regiöes do Estado de Säo Paulo, Brasil, 1984 / Etiologic study of acute haemorrhagic conjunctivitis in regions of Säo Paulo State, Brasil, 1984

Nos meses de janeiro a março de 1983 e de 1984 ocorreram sucessivamente duas epidemias de conjuntivite hemorrágica aguda (C.H.A.) no Estado de Säo Paulo, a primeira atingindo exclusivamente a área litorânea e a segunda, mais extensa, abrangendo também regiöes do planalto. A presente investigaçäo apresenta dados sobre aspectos etiológicos da epidemia de C.A.H. ocorrida em 1984. Foram examinadas amostras pareadas de soro de 73 pacientes para a pesquisa de anticorpos e amostras da secreçäo conjuntival de 179 casos com C.H.A., para a tentativa de isolamento de vírus provenientes de diferentes regiöes do Estado de Säo Paulo. Houve conversäo sorológica em 45,2% dos 73 pacientes examinados e presença de anticorpos específicos para EV-70 sem conversäo sorológica em outros 19,2%. As proporçöes mais elevadas de casos positivos situaram-se entre pacientes maiores de 20 anos, com taxas de 70,6% para o grupo etário de 20 a 29 anos, de 55,6% na faixa de 30 a 39 anos e de 72,7% em maiores de 40 anos. Foram isoladas de amostras de secreçäo conjuntival 7 cepas de adenovírus, 1 de herpes simples e 1 de EV-70. Nenhum dos soros pareados examinados foi positivo para adenovirus e, nos casos em que esses vírus foram isolados, näo foi possível obter soros pareados para a comprovaçäo sorológica de infecçäo. Os resultados obtidos confirmam a participaçäo de EV-70 nessa epidemia. Näo foram identificadas complicaçöes neurológicas associadas à infecçäo pelo EV-70

Presumptive rapid diagnosis of parvovirus infection in patients with Erythema infectiosum-like illness

In September 1987 an outbreak of exanthematous illness ressembling erythma infectiosum occurres at an elementary school of Säo Paulo city. Attempts to isolate virus from the nasofaryngeal secretion and urine and serum samples collected from the ill children in acute phase of illness resulted negative. Nevertheless, parvovirus-like particles of about 24 nm in diameter were observed by negative staining electron microscopy in concentraded urine of seven out of eight ill patients and in nasopharyngeal secretion of one out of four patients. No similar viral particle was observed in concentred urine samples collected on the same occasion from their classmates without evident signs of illness. This is a proposal of an alternative test for a rapid and sensitive presumptive diagnosis of human parvovirus infection