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Mucosal Antibody Response to COVID-19 mRNA Vaccines Depends on Prior Infection

Injected COVID-19 mRNA vaccines alone were ineffective at producing mucosal antibody responses, according to a recent study that suggested seeking new strategies such as intranasal vaccines.

COVID-19 mRNA vaccination produced a mucosal antibody response in people with prior SARS-CoV-2 infection, but the response was minimal in those who were not previously infected with the virus, a recent study found.

The study, published in Nature, included 29 adult study participants, including 18 (62%), who were infected with SARS-CoV-2 prior to vaccination and 11 (38%) who had no history of infection and were seronegative prior to vaccination.

Serum and saliva samples were collected before and after vaccination. Investigators measured anti-SARS-CoV-2 spike binding IgG titers in serum samples and anti-SARS-CoV-2 spike IgG, secretory IgA (SIgA), and nucleoprotein (NP) SIgA titers in saliva.

“Our results suggest mucosal SIgA responses induced by mRNA vaccination are impacted by pre-existing immunity,”the authors, led by Kaori Sano, PhD, DVM of the Icahn School of Medicine at Mount Sinai, wrote. “Indeed, vaccination induced a minimal mucosal SIgA response in individuals without pre-exposure to SARS-CoV-2 while SIgA induction after vaccination was more efficient in patients with a history of COVID-19.”

After vaccination, serum and mucosal anti-spike antibody titers significantly increased in both study groups. But mucosal anti-NP IgA titers did not not increase in either group after vaccination. An anti-NP SIgA response was seen in seropositive study participants, but it was not boosted by vaccination and waned over time, the study indicated.

The study found that 16 of the 18 participants who were previously infected with SARS-CoV-2 presented peak SIgA titers above the cut-off value (mean+3 standard deviation for area under the curve). That compares with 6 of 11 seronegative study participants.

“Our results support observations from other groups suggesting that intramuscular mRNA vaccination can induce SIgA antibodies in saliva under certain circumstances,” the authors, led by Kaori Sano, PhD, DVM of the Icahn School of Medicine at Mount Sinai, wrote. “Our data further suggest that vaccination alone can induce a weak mucosal SIgA response in individuals without pre-existing mucosal antibody response to SARS-CoV-2, although SIgA induction is more efficient in individuals with pre-existing mucosal antibody response to SARS-CoV-2 elicited by COVID-19.”

The study authors noted that it remains unclear the mechanism by which the injected mRNA vaccines induced a mucosal SIgA response. It is possible that the vaccines boosted pre-existing mucosal immunity in those who were previously infected. SIgA responses observed among seronegative participants could have been related to immune memory elicited by other human coronaviruses.

Further research is needed to determine whether vaccination may lead previously infected individuals to mount mucosal SIgA antibody levels sufficient to provide protection from disease and to determine the level needed to prevent infection or transmission, the study authors noted.

“(V)accination strategies, such as intranasal vaccines like NDV-HXP-S, that could successfully induce SIgA, should be sought for the control of SARS-CoV-2,” the authors wrote. “Further studies are needed to reveal the detailed mechanism of mucosal antibody induction by mRNA vaccination, determine SIgA titers that would provide sterilizing immunity, and evaluate the SIgA antiviral function in comparison to monomeric IgA.”

Corresponding author Florian Krammer, PhD, a professor of microbiology at Icahn School of Medicine at Mount Sinai, posted a link to the study on Twitter, saying “Injected mRNA vaccines are not efficient in inducing mucosal immunity. We need new vaccines!”

Previous research has demonstrated that intranasal COVID-19 vaccines may be more effective than injected vaccines in protecting against SARS-CoV-2 infection.