Future COVID-19 control requires vaccines that induce better mucosal immunity

In a recent study posted on medrex sib*Preprint server, French researchers investigated the relationship between long-term immunoglobulin (Ig)-A responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and impaired taste and smell.

study: Association between long-lasting systemic and mucosal SARS-CoV-2 IgA responses and persistent olfactory and gustatory disturbancesImage Credit: Huen Structure Bio / Shutterstock

The persistence of prolonged coronavirus disease 2019 (COVID-19) symptoms (long-term COVID) is a serious health concern among infected patients. Multiple organs and systems contribute to a highly variable clinical appearance. During the early stages of the COVID-19 pandemic, there was a significantly higher incidence of olfactory and gustatory abnormalities with qualitative or quantitative alterations. Prolonged viral clearance, autoimmunity, and inflammation-related tissue damage may be involved. Moreover, recent studies have shown persistence of humoral responses to SARS-CoV-2. The potential of the mucosal humoral compartment in identifying prognostic indicators also needs thorough investigation.

About research

In the current study, researchers investigated anti-SARS-CoV-2 IgA responses in serum and saliva of moderate COVID-19 and uninfected controls over a one-year period.

The team selected 133 out of 400 volunteers who completed the entire longitudinal follow-up based on participant eligibility, lack of new SARS-CoV-2 infection at follow-up, and quantity/quality of saliva samples. chose a person. At each follow-up visit, participants’ clinical status was assessed. Anti-SARS-CoV-2 IgA responses were assessed in blood and saliva from people with persistent olfactory or taste problems <1 year or >1 year after acute infection with the SARS-CoV-2 Wuhan strain.

result

At enrollment (V1), the team noted a median symptom onset of 1.5 months. A specific her IgA response to the SARS-CoV-2 spike was detected in the sera of nearly all previously infected individuals. IgA antibodies specifically targeted the SARS-CoV-2 spike/receptor binding domain (RBD) over the nucleocapsid (N) and spike/N-terminal domain (NTD). Compared to V1, the IgA signal he decreased dramatically after 6 months (V2). antigenThe mean anti-N IgA titers at 6 months were below the positive threshold. Anti-NIgA tended to decline between 6 and 12 months after cohort inclusion, with a negative modeling slope corresponding to a daily decrease of 0.21‰, but no response to all other targets. induced IgA titers remained stable.

Over time, total Ig responses to Spike/RBD increased and total Ig responses to N decreased. Serum-neutralizing activity against SARS-CoV-2 BetaCoV/France/IDF0372/2020 strain persisted for 16 months post-infection. The correlation between serum neutralization titers and serum anti-spike/NTD IgA at V1 was positive. Serum neutralizing titers were associated with serum antispike IgA and serum antispike/NTD IgA levels ≥6 months after infection. More than 1 year after SARS-CoV-2 infection (V3) and in the absence of immunity, serum neutralization titers continued to correlate with anti-spike IgA serum levels. Overall, the team found that the development of high anti-SARS-CoV-2 spike IgA serological titers was strongly associated with serum neutralization titers, despite an initial decline 6 months after infection. found to persist up to 16 months after infection.

In V1, we found unique anti-SARS-CoV-2 IgA in the saliva of infected individuals, as opposed to the saliva of healthy individuals. These antibodies attacked the entire viral spike and targeted the spike/RBD rather than the spike/NTD, but not the nucleocapsid. In her first 6 months, the amount of her IgA in saliva decreased dramatically for all targets. A linear mixed model revealed a negative slope corresponding to daily declines of 1.16‰ for his IgA concentration in S, 0.89‰ for spike/RBD and 0.90‰ for spike/NTD. Comparable reductions were seen against these viral targets between 6 and 12 months.

A year later, a significant number of COVID-19 patients remained symptomatic, particularly problems with taste and smell. The team found that patients with persistent olfactory and gustatory impairments had higher anti-SARS-CoV-2 IgA titers in V1, specifically targeting spikes/NTDs in saliva samples but not in serum samples. Spike NTD specificity was positively correlated with higher serum neutralization titers and thus may be a clinically relevant IgA target.

Conclusion

The results of this study highlight distinct kinetics and levels of IgA titers against SARS-CoV-2. spike protein In post-infection serum and saliva samples, the former persisted up to 16 months after the initial drop and the latter disappeared after 6 months.Antigen specificity exhibited by anti-SARS-CoV-2 IgA revealed spike/NTD as a key target, and anti-spike/NTD IgA serum levels and Neutralizing antibody titer. A correlation was also found between salivary anti-spike/NTD IgA levels and long-term persistence of taste and smell problems.

Because breakthrough infections have been found to be associated with IgA levels, IgA synthesis may be important in managing infections locally and avoiding transmission from vaccinees. I have. Therefore, future COVID-19 control will require the most effective vaccine platform or delivery route to induce mucosal immunity, as demonstrated in preclinical studies.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .