ABSTRACT
BACKGROUND: Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015-2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. METHOD(S): We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. FINDINGS: We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015-2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40.0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1.0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. INTERPRETATION: The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. FUNDING: AstraZeneca and Sanofi.Copyright © 2023 Elsevier Ltd. All rights reserved.
ABSTRACT
There is abundant epidemiological data indicating that the incidence of severe cases of coronavirus disease (COVID-19) is significantly higher in males than females worldwide. Moreover, genetic variation at the X-chromosome linked TLR7 gene has been associated with COVID-19 severity. It has been suggested that the sex-biased incidence of COVID-19 might be related to the fact that TLR7 escapes X-chromosome inactivation during early embryogenesis in females, thus encoding a doble dose of its gene product compared to males. We analyzed TLR7 expression in two acute phase cohorts of COVID-19 patients that used two different technological platforms, one of them in a multi-tissue context including saliva, nasal, and blood samples, and a third cohort that included different post-infection timepoints of long-COVID-19 patients. We additionally explored methylation patterns of TLR7 using epigenomic data from an independent cohort of COVID-19 patients stratified by severity and sex. In line with genome-wide association studies, we provide supportive evidence indicating that TLR7 has altered CpG methylation patterns and it is consistently downregulated in males compared to females in the most severe cases of COVID-19.
Subject(s)
COVID-19 , Coronavirus Infections , Coronavirus , COVID-19/complications , COVID-19/epidemiology , COVID-19/genetics , Coronavirus/genetics , Coronavirus/metabolism , DNA Methylation , Epigenomics , Female , Genome-Wide Association Study , Humans , Male , Toll-Like Receptor 7/genetics , Transcriptome , Post-Acute COVID-19 SyndromeSubject(s)
BNT162 Vaccine/adverse effects , Drug Eruptions/etiology , Skin Diseases, Vesiculobullous/chemically induced , Aged , Aged, 80 and over , COVID-19/prevention & control , Drug Eruptions/metabolism , Drug Eruptions/pathology , Humans , Male , Skin Diseases, Vesiculobullous/metabolism , Skin Diseases, Vesiculobullous/pathologyABSTRACT
Community-acquired pneumonia (CAP) continues to be an important cause of morbidity and mortality in adults. The aim of this study is to update the practical prevention guide for CAP through vaccination in Spain developed in 2016 and updated in 2018, based on available vaccines and evidence through bibliographic review and expert opinion. The arrival of COVID-19 as a new cause of CAP and the recent availability of safe and effective vaccines constitutes the most significant change. Vaccines against pneumococcus, influenza, pertussis and COVID-19 can help to reduce the burden of disease from CAP and its associated complications. The available evidence supports the priority indications established in this guide, and it would be advisable to try to achieve a widespread dissemination and implementation of these recommendations in routine clinical practice.
Subject(s)
COVID-19 , Community-Acquired Infections , Pneumonia, Pneumococcal , Adult , Community-Acquired Infections/prevention & control , Humans , Pneumococcal Vaccines , Pneumonia, Pneumococcal/prevention & control , SARS-CoV-2 , VaccinationABSTRACT
The year 2020, the first year of the COVID-19 pandemic, has launched an unprecedented effort in the search for a vaccine against SARS-CoV-2. The development of more than 250 vaccine candidates has begun, of which three have already been approved by European regulatory agencies. The strategies to develop them are varied, some vaccines have opted for a classical approach such as live attenuated virus, inactivated virus or viral subunit vaccines. In other cases, newer strategies have been employed, such as mRNA vaccines and the use of viral vectors. Among the most prominent vaccines are Moderna and Pfizer, both mRNA;Astra Zeneca and the Gamelaya Viral Vector Research Institute’s vaccines;the Sinovac inactivated virus vaccine and the Novavax subunit vaccine. All these vaccines use as antigen the spicular protein (Spike [S]) of the coronavirus. This article reviews the main vaccines against COVID-19 taking into account their mechanism of action, administration guideline, safety profile and efficacy.
Subject(s)
Antiviral Agents , COVID-19 , Antiviral Agents/therapeutic use , Humans , Macrophages , Monocytes , SARS-CoV-2ABSTRACT
The year 2020, the first year of the COVID-19 pandemic, has launched an unprecedented effort in the search for a vaccine against SARS-CoV-2. The development of more than 250 vaccine candidates has begun, of which three have already been approved by European regulatory agencies. The strategies to develop them are varied, some vaccines have opted for a classical approach such as live attenuated virus, inactivated virus or viral subunit vaccines. In other cases, newer strategies have been employed, such as mRNA vaccines and the use of viral vectors. Among the most prominent vaccines are Moderna and Pfizer, both mRNA;Astra Zeneca and the Gamelaya Viral Vector Research Institute’s vaccines;the Sinovac inactivated virus vaccine and the Novavax subunit vaccine. All these vaccines use as antigen the spicular protein (Spike [S]) of the coronavirus. This article reviews the main vaccines against COVID-19 taking into account their mechanism of action, administration guideline, safety profile and efficacy. © 2020, Ediciones Ergon SA. All rights reserved.