Saliva is suitable for SARS-CoV-2 antibodies detection after vaccination: A rapid systematic review

Abstract

Since the introduction of efficient vaccines anti-SARS-CoV-2, antibody quantification becomes increasingly useful for immunological monitoring and COVID-19 control. In several situations, saliva samples may be an alternative to the serological test. Thus, this rapid systematic review aimed to evaluate if saliva is suitable for SARS-CoV-2 detection after vaccination. For this purpose, search strategies were applied at EMBASE, PubMed, and Web of Science. Studies were selected by two reviewers in a two-phase process. After selection, 15 studies were eligible and included in data synthesis. In total, salivary samples of approximately 1,080 vaccinated and/or convalescent individuals were analyzed. The applied vaccines were mostly mRNA-based (BioNTech 162b2 mRNA/Pfizer and Spikevax mRNA-1273/Moderna), but recombinant viral-vectored vaccines (Ad26. COV2. S Janssen - Johnson & Johnson and Vaxzevria/Oxford AstraZeneca) were also included. Different techniques were applied for saliva evaluation, such as ELISA assay, Multiplex immunoassay, flow cytometry, neutralizing and electrochemical assays. Although antibody titers are lower in saliva than in serum, the results showed that saliva is suitable for antibody detection. The mean of reported correlations for titers in saliva and serum/plasma were moderate for IgG (0.55, 95% CI 0.38-9.73), and weak for IgA (0.28, 95% CI 0.12-0.44). Additionally, six out of nine studies reported numerical titers for immunoglobulins detection, from which the level in saliva reached their reference value in four (66%). IgG but not IgA are frequently presented in saliva from vaccinated anti-COVID-19. Four studies reported lower IgA salivary titers in vaccinated compared to previously infected individuals, otherwise, two reported higher titers of IgA in vaccinated. Concerning IgG, two studies reported high antibody titers in the saliva of vaccinated individuals compared to those previously infected and one presented similar results for vaccinated and infected. The detection of antibodies anti-SARS-CoV-2 in the saliva is available, which suggests this type of sample is a suitable alternative for monitoring the population. Thus, the results also pointed out the possible lack of mucosal immunity induction after anti-SARS-CoV-2 vaccination. It highlights the importance of new vaccination strategies also focused on mucosal alternatives directly on primary routes of SARS-CoV-2 entrance.

Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022336968, identifier CRD42022336968.

Keywords: COVID-19 vaccines; IgA; IgG; SARS-CoV-2; antibodies; saliva.

Figure 1

Flow diagram of literature search and selection criteria based on PRISMA 2020.

Figure 2

Characteristics of studies and antigen analysis in salivary samples. (A) Graphic showing the methods assessed and assays applied for saliva analysis and the number of studies using each type. (B) Graphic showing different immunoglobulins assessed and the number of studies assessing each type. (C) Graphic showing different antigen assessed for binding reaction and the number of studies assessing each type. CLIA, chemiluminescence immunoassay; ECLIA, electro-chemiluminescence immunoassay; ELISA, Enzyme-linked immunosorbent assay; FC, Flow Cytometry; IgA, Immunoglobulin A; IgG, immunoglobulin G; IgM,Immunoglobulin M; MB, Multiplex Bead; NA, Neutralizing activity; NC, nucleocapsid; NR, Not reported; BD, receptor binding domain; S, spike protein; Total Ig, Total immunoglobulins.

Figure 3

Correlations analysis regarding antibodies detection in serum/plasma and saliva. (A) Mean of correlation coefficients between antibodies detection in serum/plasma and saliva for IgG and IgA. (B) Mean of correlation coefficients between antibodies detection separated by antigen-antibody reaction for IgG and IgA. IgA, Immunoglobulin A; IgG, immunoglobulin G; RBD, receptor binding domain; S, spike protein; Total Ig, Total immunoglobulins.

Figure 4

The proportion of studies on secondary outcomes. (A) Graphic showing the proportion of studies reporting results on IgA comparison between vaccinated and previous infected individuals (B) Graphic showing the proportion of studies reporting results on IgG comparison between vaccinated and previous infected individuals. IgA, immunoglobulin A; IgG, Immunoglobulin G.