COVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.
In March 2020, the World Health Organization (WHO) declared a global health emergency—the coronavirus disease 2019 (COVID-19) pandemic. Since then, the development and implementation of vaccines against the virus amidst emerging cases of re-infection has prompted researchers to work towards understanding how immunity develops and is sustained. Serological testing has been instrumental in monitoring the development and persistence of antibodies against SARS-CoV-2 infection, however inconsistencies in detection have been reported by different methods. As serological testing becomes more commonplace, it is important to establish widespread and repeatable processes for monitoring vaccine efficacy. Therefore, we present enzyme linked immunosorbent assays (ELISAs) compatible for antibody detection in saliva as highly accurate, efficacious, and scalable tools for studying the immune response in individuals vaccinated against SARS-CoV-2.
BackgroundDeveloping an understanding of the antibody response, seroprevalence, and seroconversion from natural infection and vaccination against SARS-CoV-2 will give way to a critical epidemiological tool to predict reinfection rates, identify vulnerable communities, and manage future viral outbreaks. To monitor the antibody response on a larger scale, we need an inexpensive, less invasive, and high throughput method.MethodsHere we investigate the use of oral mucosal fluids from individuals recovered from SARS-CoV-2 infection to monitor antibody response and persistence over a 12-month period. For this cohort study, enzyme-linked immunosorbent assays (ELISAs) were used to quantify anti-Spike(S) protein IgG antibodies in participants who had prior SARS-CoV-2 infection and regularly (every 2-4 weeks) provided both serum and oral fluid mucosal fluid samples for longitudinal antibody titer analysis.ResultsIn our study cohort (n=42) with 17 males and 25 females with an average age of 45.6 +/- 19.3 years, we observed no significant change in oral mucosal fluid IgG levels across the time course of antibody monitoring. In oral mucosal fluids, all the participants who initially had detectable antibodies continued to have detectable antibodies throughout the study.ConclusionsBased on the results presented here, we have shown that oral mucosal fluid-based assays are an effective, less invasive tool for monitoring seroprevalence and seroconversion, which offers an alternative to serum-based assays for understanding the protective ability conferred by the adaptive immune response from viral infection and vaccination against future reinfections.
Saliva specimens offer practical advantages over serum specimens for studying SARS-CoV-2 immunity following natural infections or vaccination. Salivary anti-spike (S)-protein immunoglobulin G (IgG) antibody titers are quantifiable by ELISA with high sensitivity and specificity and robustly correlated with serum titers. Our longitudinal prospective study enrolled participants who received two-dose regimen vaccination with either mRNA-1273 or BNT162b2 vaccines, and salivary anti-S-protein IgG titers were measured at intervals for its duration. Subsequently, participants received homologous mRNA-1273 (n=28) and BNT162b2 (n=29) booster vaccines and enrolled in the booster study. Participants performed self-collection of saliva specimens with the OraSure device at predetermined time intervals for each cohort. Salivary anti-S-protein IgG titers varied between participants following the second dose; titers waned from their peak 9 to 150-fold in the mRNA-1273 cohort and 7 to 105-fold in the BNT162b2 cohort. The booster dose elicited a 2 to 238-fold increase in the mRNA-1273 cohort and a 20 to 255-fold increase in the BNT162b2 cohort from the lowest titer. These results replicate the antibody waning and recall trends following second and third doses reported in larger studies using serum specimens, supporting the use of non-invasive saliva specimens to monitor antibody titers during future epidemics or vaccination campaigns.
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