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COVID-19 mRNA vaccines stimulated mucosal immunity in people previously infected with SARS-CoV-2, but generated only a tiny amount of immunity in people who had never been infected, according to a cohort study using data from the French CoviCompare trials.

Among trial participants who received the Moderna mRNA-1273 (Spikevax) vaccine in early to mid 2021, SARS-CoV-2 spike-specific saliva IgA levels were significantly higher in those with previous infection compared with the most responsive SARS-CoV-2-naive participants at day 180 (P<0.001), reported Guy Gorochov, MD, PhD, of Sorbonne University in Paris, and colleagues in .

In participants without prior infection, compared with day 1, increases of specific salivary IgA levels were smaller, especially after vaccination with the Pfizer-BioNTech BNT162b2 (Comirnaty) vaccine, reaching statistical significance only at day 57 (P=0.01).

SARS-CoV-2 spike-specific IgG saliva levels increased after one or two shots in participants with previous infection and those who never had infection.

"Until now, there was still a considerable controversy in the literature regarding the capacity of intramuscular mRNA vaccination to induce a mucosal immune response," Gorochov told 乌鸦传媒 in an email. "In this study, we show that current vaccines can, at best, induce traces of specific antibodies in the saliva in individuals that were never infected by the virus before vaccination."

"After intramuscular vaccination, we did not expect to detect SARS-CoV-2-specific secretory IgA antibodies" in the saliva of SARS-CoV-2-naive people, he said. "Since the vaccine is injected in muscles, we expected an appearance of specific antibodies in the serum, but not in secretory body fluids for induction of a protective barrier effect."

"It is very important to underline that a clear stimulation of mucosal immunity [was] only observed in vaccinees with prior SARS-CoV-2 infection," he added, despite the detection of small amounts of spike-specific salivary IgA in vaccinated SARS-CoV-2-naive participants.

"Nasal delivery of vaccines might one day improve their local efficacy," Gorochov noted. "Further studies would then be needed to address the association between local secretory IgA levels and prevention of infection or transmission of SARS-CoV-2."

IgA is the of the respiratory and intestinal tracts, whereas IgG is the principal isotype found in serum and extracellular fluid. IgA is monomeric in human serum but is also produced locally in mucosal tissues mostly under dimeric or even polymeric forms and released as secretory IgA, the authors wrote. Monomeric IgA is also present in saliva following passive transport from blood.

The mRNA-1273 vaccine appeared to elicit a stronger immune response than the BNT162b2 vaccine. Among the SARS-CoV-2-naive patients, serum anti-spike IgG and IgA levels were significantly higher among people who received the mRNA-1273 vaccine (P<0.001 for all comparisons).

This study included 180 patients from the CoviCompare M trial and 267 patients from the CoviCompare P trial, enrolled from February 19 to June 8, 2021 in France. After exclusions, 427 participants were included in this study. Of these, 120 had a documented SARS-CoV-2 infection at least 5 months before receiving a single dose of the BNT162b2 vaccine. The remaining 307 patients had received two doses of either the mRNA-1273 vaccine or the BNT162b2 vaccine and had no prior documented SARS-CoV-2 infection. The median age of participants was 68 years, and 53.4% were men.

The researchers measured total saliva IgA and IgG, SARS-CoV-2 spike- and nucleocapsid-specific serum antibodies, and secretory SARS-CoV-2-specific IgA using enzyme-linked immunosorbent assay (ELISA) tests. Ultrasensitive digital ELISA technology was used to measure and compare spike-specific serum and salivary IgG and IgA levels.

The main limitation of the study was that the authors were unable to determine whether the increase in specific secretory IgA in infection-naive individuals could be attributable to asymptomatic or seronegative exposures to SARS-CoV-2, Gorochov said.

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