Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination

Abstract

Previous studies have shown that mRNA COVID-19 vaccines are highly effective at preventing SAR-CoV-2 infection by generating an immune response, which in part produces SARS-CoV-2 IgG antibodies in serum. In this study, we hypothesized that COVID-19 vaccines may elicit production of SARS-CoV-2 IgG antibodies in the upper respiratory tract, such as in oral and nasal mucosal fluid. To test that hypothesis, we enrolled 114 participants within 3-7 days of receiving the first dose of the Moderna mRNA COVID-19 vaccine and collected oral mucosal fluid samples on days 5, 10, 15, and 20 after each vaccine dose. Of participants naive to SARS-CoV-2 (n = 89), 79 (85.4%) tested positive for SARS-CoV-2 IgG antibodies by time point 2 (10 days +/-2 days after first vaccine dose), and 100% tested positive for SARS-CoV-2 IgG by time point 3 (15 days +/- 2 days after first vaccine dose). Additionally, we collected paired oral mucosal fluid and anterior nares samples from 10 participants who had received both vaccine doses. We found that participants had an average SARS-CoV-2 IgG antibody concentration of 2496.0 +/- 2698.0ng/mL in nasal mucosal fluid versus 153.4 +/- 141.0ng/mL in oral mucosal fluid. Here, we demonstrate detection and longitudinal persistence of SARS-CoV-2 IgG antibodies in upper respiratory tract specimens following COVID-19 mRNA vaccination. A high concentration of IgG targeting viral spike protein in the upper respiratory system may play an unexplored role in the prevention of SARS-CoV-2 infection and deserves further investigation.

SARS-CoV-2 Specific IgG Antibodies Persist Over a 12-Month Period in Oral Mucosal Fluid Collected From Previously Infected Individuals

“…As more and more people become vaccinated, we are using the lessons learned from this study to monitor the persistence of antibodies in oral mucosal fluids against the Moderna or Pfizer vaccine in an ongoing year long clinical trial. Our early results are encouraging as we observe an increasing antibody titer in vaccinated participants consistent with what we observed in this cohort ( 10 ).…”

“…To that end, OraSure Technologies ® has developed an oral specimen collection device (OSCD) and a total antibody ELISA for use with oral mucosal fluid collected from this device. An earlier study from our group showed that it is possible to quantify the antibody titers from oral mucosal fluids collected by the OSCD ( 10 ). It should be noted that, at present, the relationship between concentrations of antibody and possible immune protection is not well understood.…”

Prevention of host-to-host transmission by SARS-CoV-2 vaccines

“…16,17 Additionally, IgA and IgG neutralising antibodies, including highly effective secreted dimeric IgA, have been observed in the saliva of patients vaccinated with BNT162b1 or mRNA-1273. 15,[18][19][20] These studies show variable capacity among the parenteral vaccines to induce sterilising immunity at the mucosa, with ChAdOx1 vaccine being potentially less effective than the mRNA vaccines. Factors potentially influencing whether these vaccines induce mucosal sterilising immunity include the mechanism of the vaccine and the quantity and quality of circulating neutralising antibodies generated.…”

The germinal centre B cell response to SARS-CoV-2

“…Another key unanswered question is whether SARS-CoV-2 vaccination induces a B cell response in mucosal tissues. While SARS-CoV-2-specific antibodies are detectable in mucosal compartments such as the saliva and breast milk following vaccination, it is unclear whether these antibodies are a product of a local B cell response or how long they persist 166 – 168 . SARS-CoV-2 vaccines are administered intramuscularly and therefore are unlikely to induce sufficient levels of antigen expression or inflammation in mucosal tissues to support a local GC response.…”