Antigenic and genetic variability of human metapneumoviruses

Human metapneumovirus (HMPV) is a member of the subfamily Pneumovirinae within the family Paramyxo- viridae. Other members of this subfamily, respiratory syncytial virus and avian pneumovirus, can be divided into subgroups on the basis of genetic or antigenic differences or both. For HMPV, the existence of different genetic lineages has been described on the basis of variation in a limited set of available sequences. We address the antigenic relationship between genetic lineages in virus neutralization assays. In addition, we analyzed the genetic diversity of HMPV by phylogenetic analysis of sequences obtained for part of the fusion protein (n = 84) and the complete attachment protein open reading frames (n = 35). On the basis of sequence diversity between attachment protein genes and the differences in virus neutralization titers, two HMPV serotypes were defined. Each serotype could be divided into two genetic lineages, but these did not reflect major antigenic differences

Decreased point prevalence of Haemophilus influenzae type b (Hib) oropharyngeal colonization by mass immunization of Brazilian children less than 5 years old with Hib polyribosylribitol phosphate polysaccharide-tetanus toroid conjugate vaccine in combination with diphtheria-tetanus toxoids-pertussis vaccine

A protective herd effect has been described after susceptible populations of children are vaccinated with conjugate Haemophilus influenzae type b (Hib), Hib carriage was studied in children aged 6-24 months attending day care centers in two cities in southern Brazil (Curitiba and Porto Alegre), in Curitiba, routine immunization with Hib polyribosylribitol phosphate polysaccharide-tetanus toroid conjugate vaccine (PRP-T) in combination with diphtheria-tetanus toxoids-pertussis vaccine (PRP-T/DTP) has been offered since September 1996; DTP vaccine alone is routinely given in Porto Alegre, Children in Porto Alegre (n = 643) were 8 times less likely to have received adequate Hib vaccination and 4 times more likely to be Hib carriers than children in Curitiba (n = 647; i.e., point prevalence of oropharyngeal colonization, 4.8% vs. 1.2%). Point prevalence of carriage with non-type b or other nontypeable Hi was similar in children of both cities, There was a vaccination effect on carriage rates in children who received a primary 3-dose series, independent of the booster dose, suggesting that a booster may be unnecessary to induce population protection.Pasteur Merieux Connaught Brasil, Dept Med, BR-04552905 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilSecretaria Estado Saude São Paulo, Inst Adolfo Lutz, Seccao Bacteriol, São Paulo, BrazilSanta Casa Misericordia São Paulo, Fac Ciencias Med, Dept Patol, São Paulo, BrazilSecretaria Municipal Saude Curitiba, Dept Epidemiol, Curitiba, Parana, BrazilSecretaria Municipal Saude Porto Alegre, Dept Epidemiol, Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc

A Prospective Study of Key Correlates for Household Transmission of Severe Acute Respiratory Syndrome Coronavirus 2

Background: Randomized controlled trials evaluated monoclonal antibodies for the treatment (Study 2067) and prevention (Study 2069) of coronavirus disease 2019 (COVID-19). Household contacts of the infected index case in Study 2067 were enrolled in Study 2069 and prospectively followed; these cohorts provided a unique opportunity to evaluate correlates of transmission, specifically viral load. Methods: This post hoc analysis was designed to identify and evaluate correlates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, adjusting for potential confounding factors related to source SARS-CoV-2 viral load and risk of SARS-CoV-2 acquisition in this population. Correlates of transmission were evaluated in potential transmission pairs (any infected household member plus susceptible household contact). Results: In total, 943 participants were included. In multivariable regression, 2 potential correlates were determined to have a statistically significant (P <. 05) association with transmission risk. A 10-fold increase in viral load was associated with a 40% increase in odds of transmission; sharing a bedroom with the index participant was associated with a 199% increase in odds of transmission. Conclusions: In this prospective, post hoc analysis that controlled for confounders, the 2 key correlates for transmission of SARS-CoV-2 within a household are sharing a bedroom and increased viral load, consistent with increased exposure to the infected individual

The Dilemma of Influenza Vaccine Recommendations when Applied to the Tropics: The Brazilian Case Examined Under Alternative Scenarios

Since 1999 the World Health Organization issues annually an additional influenza vaccine composition recommendation. This initiative aimed to extend to the Southern Hemisphere (SH) the benefits—previously enjoyed only by the Northern Hemisphere (NH)—of a vaccine recommendation issued as close as possible to the moment just before the onset of the influenza epidemic season. A short time between the issue of the recommendation and vaccine delivery is needed to maximize the chances of correct matching between putative circulating strains and one of the three strains present in the vaccine composition. Here we compare the effectiveness of the SH influenza vaccination adopted in Brazil with hypothetical alternative scenarios defined by different timings of vaccine delivery and/or composition. Scores were based on the temporal overlap between vaccine-induced protection and circulating strains. Viral data were obtained between 1999 and 2007 from constant surveillance and strain characterization in two Brazilian cities: Belém, located at the Equatorial region, and São Paulo, at the limit between the tropical and subtropical regions. Our results show that, among currently feasible options, the best strategy for Brazil would be to adopt the NH composition and timing, as in such case protection would increase from 30% to 65% (p<.01) if past data can be used as a prediction of the future. The influenza season starts in Brazil (and in the equator virtually ends) well before the SH winter, making the current delivery of the SH vaccination in April too late to be effective. Since Brazil encompasses a large area of the Southern Hemisphere, our results point to the possibility of these conclusions being similarly valid for other tropical regions

Examining protective effects of SARS-CoV-2 neutralizing antibodies after vaccination or monoclonal antibody administration

While new vaccines for SARS-CoV-2 are authorized based on neutralizing antibody (nAb) titer against emerging variants of concern, an analogous pathway does not exist for preventative monoclonal antibodies. In this work, nAb titers were assessed as correlates of protection against COVID-19 in the casirivimab + imdevimab monoclonal antibody (mAb) prevention trial (ClinicalTrials.gov #NCT4452318) and in the mRNA-1273 vaccine trial (ClinicalTrials.gov #NCT04470427). In the mAb trial, protective efficacy of 92% (95% confidence interval (CI): 84%, 98%) is associated with a nAb titer of 1000 IU50/ml, with lower efficacy at lower nAb titers. In the vaccine trial, protective efficacies of 93% [95% CI: 91%, 95%] and 97% (95% CI: 95%, 98%) are associated with nAb titers of 100 and 1000 IU50/ml, respectively. These data quantitate a nAb titer correlate of protection for mAbs benchmarked alongside vaccine induced nAb titers and support nAb titer as a surrogate endpoint for authorizing new mAbs

Subcutaneous REGEN-COV Antibody Combination to Prevent Covid-19

BACKGROUND REGEN-COV (previously known as REGN-COV2), a combination of the monoclonal antibodies casirivimab and imdevimab, has been shown to markedly reduce the risk of hospitalization or death among high-risk persons with coronavirus disease 2019 (Covid-19). Whether subcutaneous REGEN-COV prevents severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent Covid-19 in persons at high risk for infection because of household exposure to a person with SARS-CoV-2 infection is unknown. METHODS We randomly assigned, in a 1:1 ratio, participants (=12 years of age) who were enrolled within 96 hours after a household contact received a diagnosis of SARSCoV- 2 infection to receive a total dose of 1200 mg of REGEN-COV or matching placebo administered by means of subcutaneous injection. At the time of randomization, participants were stratified according to the results of the local diagnostic assay for SARS-CoV-2 and according to age. The primary efficacy end point was the development of symptomatic SARS-CoV-2 infection through day 28 in participants who did not have SARS-CoV-2 infection (as measured by reverse-transcriptase- quantitative polymerase-chain-reaction assay) or previous immunity (seronegativity). RESULTS Symptomatic SARS-CoV-2 infection developed in 11 of 753 participants in the REGEN-COV group (1.5%) and in 59 of 752 participants in the placebo group (7.8%) (relative risk reduction [1 minus the relative risk], 81.4%; P104 copies per milliliter) was shorter (0.4 weeks and 1.3 weeks, respectively). No dose-limiting toxic effects of REGEN-COV were noted. CONCLUSIONS Subcutaneous REGEN-COV prevented symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection in previously uninfected household contacts of infected persons. Among the participants who became infected, REGEN-COV reduced the duration of symptomatic disease and the duration of a high viral load

Impacto da vacinação de maiores de 60 anos para influenza sobre as internações e óbitos por doenças respiratórias e circulatórias em Fortaleza - CE - Brasil Influenza vaccination of individuals over the age of 60: impact on hospital admissions and deaths from respiratory and circulatory diseases in Fortaleza, Brazil

OBJETIVO: Este estudo tem por objetivo avaliar o impacto da vacina da influenza sobre internações e óbitos por doenças respiratórias e circulatórias em Fortaleza - CE. MÉTODOS: Analisaram-se os dados do Ministério da Saúde sobre óbitos (período 1995 a 2001) e internações por doenças respiratórias e circulatórias (1995 a 2003) em residentes de Fortaleza maiores de 60 anos. RESULTADOS: Ocorreram 29.867 internações por doença do aparelho respiratório. Entre 1995 e 1998, a média anual foi de 3.067,3 (desvio-padrão de 365,8) e entre 1999 e 2003 a média foi de 3.519 (desvio padrão de 195,6), sem redução significativa quando corrigida pela população. Em relação a 1998, as internações não diminuíram em 1999 (p > 0,641), em 2002 (p > 0,5), nem em 2003 (p > 0,72); reduziram em 2000 (p < 0,002) e 2001 (p < 0,0014). Reduziram-se significativamente (p < 0,05) o número de óbitos e a taxa de mortalidade geral nos anos 1999, 2000 e 2001 em relação a 1998, sem diferença entre 2000 e 2001. A distribuição mensal das internações não foi modificada pela vacinação. CONCLUSÃO: Não foram demonstrados os resultados desejados com a vacinação de idosos. Sugerem-se estudos de sazonalidade do vírus para melhor definição da época ideal para vacinação.<br>OBJECTIVE: The objective of this study was to evaluate the impact of influenza vaccination on hospital admissions and deaths from respiratory and circulatory diseases in the city of Fortaleza, located in the state of Ceará, Brazil. METHODS: Brazilian Health Ministry data regarding deaths from respiratory and circulatory diseases occurring between 1995 and 2001, as well as hospital admissions related to such diseases between 1995 among 2003, in both cases limited to residents of Fortaleza above the age of 60 years, were analyzed. RESULTS: There were 29,867 admissions for respiratory disease. Between 1995 and 1998, the mean number of annual admissions was 3067.3 (standard deviation, 365.8). Between 1999 and 2003, the average was 3519 (standard deviation, 195.6). When adjusted for the increase in population, the difference between the two periods was less than significant. From 1998 to 1999, there was no significant reduction in the number of admissions from circulatory disease (p > 0.641). Nor was there a significant reduction from 1998 to 2000 (p < 0.5) or from 1998 to 2003 (p > 0.72), although there were significant reductions in 2000 (p < 0.002) and 2001 (p < 0.0014). There was a significant reduction in the number of deaths and in overall mortality rates during 1999, 2000 and 2001 in relation to 1998 (p < 0.05), with no difference between 2000 and 2001. The monthly distribution of admissions was not altered as a result of the vaccinations. CONCLUSION: Our data show that vaccination of the elderly did not achieve the desired results. This suggests that seasonality studies are needed in order to identify the ideal time of year for such vaccinations