Mucosal Immunity

Targeted public health interventions for an emerging epidemic are essential for preventing pandemics. During 2020-2022, China invested significant efforts in strict zero-COVID measures to contain outbreaks of varying scales caused by different SARS-CoV-2 variants. Based on a multi-year empirical dataset containing 131 outbreaks observed in China from April 2020 to May 2022 and simulated scenarios, we ranked the relative intervention effectiveness by their reduction in instantaneous reproduction number. We found that, overall, social distancing measures (38% reduction, 95% prediction interval 31-45%), face masks (30%, 17-42%) and close contact tracing (28%, 24-31%) were most effective. Contact tracing was crucial in containing outbreaks during the initial phases, while social distancing measures became increasingly prominent as the spread persisted. In addition, infections with higher transmissibility and a shorter latent period posed more challenges for these measures. Our findings provide quantitative evidence on the effects of public-health measures for zeroing out emerging contagions in different contexts. China maintained a ‘zero-COVID’ policy from early in the pandemic until late 2022 that employed various public health interventions with the aim of COVID-19 containment. Here, the authors use data from 131 outbreaks in China to estimate the effects of a range of interventions against different SARS-CoV-2 variants in diverse settings.

Results of a human challenge trial in which volunteers were inoculated with SARS-CoV-2 have shed more light into the modes of transmission of the virus. The… | 16 commentaires sur LinkedIn

Physicians say they hope the needle-free jab will fuel booster demand, helping squash transmission of the pandemic virus.

Most studies of adaptive immunity to SARS-CoV-2 infection focus on peripheral blood, which may not fully reflect immune responses at the site of infection. Using samples from 110 children undergoing tonsillectomy and adenoidectomy during the COVID-19 pandemic, we identified 24 samples with evidence of previous SARS-CoV-2 infection, including neutralizing antibodies in serum and SARS-CoV-2-specific germinal center and memory B cells in the tonsils and adenoids. Single-cell B cell receptor (BCR) sequencing indicated virus-specific BCRs were class-switched and somatically hypermutated, with overlapping clones in the two tissues. Expanded T cell clonotypes were found in tonsils, adenoids and blood post-COVID-19, some with CDR3 sequences identical to previously reported SARS-CoV-2-reactive T cell receptors (TCRs). Pharyngeal tissues from COVID-19-convalescent children showed persistent expansion of germinal center and antiviral lymphocyte populations associated with interferon (IFN)-γ-type responses, particularly in the adenoids, and viral RNA in both tissues. Our results provide evidence for persistent tissue-specific immunity to SARS-CoV-2 in the upper respiratory tract of children after infection. Manthiram and colleagues analyze the peripheral blood, tonsils and adenoids in children undergoing tonsillectomy or adenoidectomy and find evidence of continued tissue-specific immunity to SARS-CoV-2 and viral RNA persistence weeks to months after acute infection.

One of the most preferable characteristics for a COVID-19 vaccine candidate is the ability to reduce transmission and infection of SARS-CoV-2, in addition to disease prevention. Unlike intramuscular vaccines, intranasal COVID-19 vaccines may offer this by generating mucosal immunity. In this open-label, randomised, multicentre, phase 3 clinical trial (CTRI/2022/02/40065; ClinicalTrials.gov: NCT05522335), healthy adults were randomised to receive two doses, 28 days apart, of either intranasal adenoviral vectored SARS-CoV-2 vaccine (BBV154) or licensed intramuscular vaccine, Covaxin®. Between April 16 and June 4, 2022, we enrolled 3160 subjects of whom, 2971 received 2 doses of BBV154 and 161 received Covaxin. On Day 42, 14 days after the second dose, BBV154 induced significant serum neutralization antibody titers against the ancestral (Wuhan) virus, which met the pre-defined superiority criterion for BBV154 over Covaxin®. Further, both vaccines showed cross protection against Omicron BA.5 variant. Salivary IgA titers were found to be higher in BBV154. In addition, extensive evaluation of T cell immunity revealed comparable responses in both cohorts due to prior infection. However, BBV154 showed significantly more ancestral specific IgA-secreting plasmablasts, post vaccination, whereas Covaxin recipients showed significant Omicron specific IgA-secreting plasmablasts only at day 42. Both vaccines were well tolerated. Overall reported solicited reactions were 6.9% and 25.5% and unsolicited reactions were 1.2% and 3.1% in BBV154 and Covaxin® participants respectively.

Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. Next-generation vaccines which are able to induce mucosal immunity in the upper respiratory to prevent or reduce infections caused by highly transmissible variants of SARS-CoV-2 are urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein, designated DelNS1-RBD4N-DAF. Immune responses and protection against virus challenge following intranasal administration of DelNS1-RBD4N-DAF vaccines were analyzed in mice and compared with intramuscular injection of the BioNTech BNT162b2 mRNA vaccine in hamsters. DelNS1-RBD4N-DAF LAIVs induced high levels of neutralizing antibodies against various SARS-CoV-2 variants in mice and hamsters and stimulated robust T cell responses in mice. Notably, vaccination with DelNS1-RBD4N-DAF LAIVs, but not BNT162b2 mRNA, prevented replication of SARS-CoV-2 variants, including Delta and Omicron BA.2, in the respiratory tissues of animals. The DelNS1-RBD4N-DAF LAIV system warrants further evaluation in humans for the control of SARS-CoV-2 transmission and, more significantly, for creating dual function vaccines against both influenza and COVID-19 for use in annual vaccination strategies. Current vaccines are less efficient in preventing infection. Here, the authors show that an intranasal vaccine (DelNS1-RBD) based on a live attenuated influenza virus induces robust levels of neutralizing antibodies and T cells and prevents replication of SARS-CoV-2 Delta and Omicron variants in respiratory tissues.

ACE2 plays fundamental roles in human physiology and disease. This review summarizes
ACE2’s functions, highlights its relationship with SARS-CoV-2, describes implications
for long COVID, and provides a framework for developing universal therapeutic strategies
against current and future SARS-CoV-2 variants by exploring the ACE2 pathway and interfering
with the spike-ACE2 interaction.

An effective nasal vaccine could stop the virus that causes COVID-19 right at its point of entry. But devising one that works has been a challenge for researchers.