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. 2023 Feb 24;11(3):534.
doi: 10.3390/vaccines11030534.

SARS-CoV-2 Breakthrough Infections after Third Doses Boost IgG Specific Salivary and Blood Antibodies

María Noel Badano  1   2 , Matias J Pereson  3 , Florencia Sabbione  1 , Irene Keitelman  1 , Natalia Aloisi  2 , Roberto Chuit  4 , María M E de Bracco  1 , Susana Fink  1 , Patricia Baré  1   2
Affiliations

SARS-CoV-2 Breakthrough Infections after Third Doses Boost IgG Specific Salivary and Blood Antibodies

María Noel Badano et al. Vaccines (Basel). .

Abstract

SARS-CoV-2 breakthrough infections, associated with waning immunity, increase systemic antibody levels. In this study, we analyzed the impact of the infection timing on the magnitude of the systemic humoral response and whether breakthrough infections also boost antibody levels in the salivary compartment. We observed that the combination of infection plus vaccination, regardless of infection timing, produced a sharp increase in systemic antibodies, which were higher in subjects infected after third doses. Moreover, despite high systemic antibody levels, breakthrough infections after dose three occurred and boosted antibody levels in the salivary compartment. These results suggest that current vaccination strategies against COVID-19 should be improved. Results also showed that determination of salivary antibodies against SARS-CoV-2 could be a valuable tool in disease prevalence studies, for the follow-up of vaccinated individuals, and to assist vaccination strategies against COVID-19, especially in settings where blood sampling cannot be fulfilled.

Keywords: IgG specific salivary antibodies; SARS-CoV-2 breakthrough infections; anti-spike antibody levels; humoral response; vaccines.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SARS-CoV-2 infection boosts humoral immunity in vaccinated individuals. (A) Systemic antibody concentrations in subjects infected with SARS-CoV-2 before vaccination (G0) or after the first (G1), second (G2), or third (G3) vaccine doses. SARS-CoV-2 spike-specific IgG antibodies were measured before vaccination (T0) and 21–30 days after the first (T1), second (T2), and third (T3) doses. For subjects infected with SARS-CoV-2 after the first (G1), second (G2), or third vaccine doses (G3), antibody concentrations were also measured 21 to 30 days after infections (ai), identified as T1ai, T2ai, and T3ai respectively. IgG anti-spike antibody concentrations (BAU/mL) with geometric means are shown. Dotted line indicates the assay detection limit (4.03 BAU/mL). p values were determined by unpaired t test or Mann–Whitney test. (B) Salivary IgG antibodies to SARS-CoV-2 were measured in cases (G3) and in uninfected control subjects vaccinated with three doses (CG), before (T3) and following breakthrough infections after the third doses (T3ai and T3c, respectively). PCR-negative saliva samples from the early stages of the pandemic were used as negative controls (NC) for reactivity. IgG anti-spike antibody concentrations (BAU/mL) with geometric means are shown. Dotted line indicates the assay detection limit (4.03 BAU/mL). p values were determined by Mann–Whitney test. (C) Correlation between matched salivary and blood SARS-CoV-2-specific IgG responses. Blood and saliva sample pairs (n = 70) from individuals infected after the third dose (G3, n = 17), and from uninfected control subjects vaccinated with three doses (CG, n = 18), were collected before (T3) and following breakthrough infections (T3ai and T3c, respectively). Correlation between specific salivary and blood antibodies was analyzed by the Spearman rank correlation test. Spearman correlation coefficient (r) and p-value are indicated.
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