Natural SARS-CoV-2 Infection Affects Neutralizing Activity in Saliva of Vaccinees

Abstract

BackgroundSARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed.Material and MethodsWe fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the “wild type” SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay.ResultsNA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV.DiscussionThe difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant.ConclusionsThe administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination.

How Do Anti-SARS-CoV-2 mRNA Vaccines Protect from Severe Disease?

“…Conversely, high levels of binding activity (presumably due to non-neutralizing anti-Spike protein IgGs) were found in the presence of high titers of both binding and neutralizing antibodies in the serum [ 3 ]. More recent works have essentially confirmed these data [ 4 , 26 , 27 ]. As a direct consequence, the levels of viral replication in oral mucosa of vaccinated and unvaccinated subjects scored similarly [ 5 , 6 ].…”

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

“…Of the included articles, 11 are longitudinal studies ( 12 , 16 , 25 – 28 , 30 , 32 , 35 – 37 ), and four are cross-sectional studies ( 29 , 31 , 33 , 34 ). All studies were published in English between 2021 and 2022.…”

“…All studies were published in English between 2021 and 2022. Five of them were conducted in Italy ( 25 , 27 , 28 , 31 , 32 ), three in United States ( 12 , 16 , 33 ), three in Germany ( 30 , 34 , 35 ), two in Canada ( 26 , 36 ), one in Croatia ( 29 ), and one in Australia ( 37 ).…”

“…Two studies reported the main conclusions on neutralization correlations (Table 1). Garziano et al (31) assessed the correlation of neutralizing activity in plasma and saliva. The reported results showed stronger coefficients for individuals who were previously infected with (r=0.52) or without (r=0.…”

“…This observation could be explained by the absence of mucosal immunity induction in vaccinated individuals, associated with a quantity of Ig issued from the crevicular fluid that was insufficient to be neutralizing. Furthermore, one dose of vaccine was able to boost an anti-SARS-CoV-2 response in previously infected individuals, whilst the third dose with a different vaccine type led to a significantly stronger response than only two doses (31,35). Although a neutralizing activity was detected in saliva, intramuscular vaccines are not proved to be effective in producing salivary effects.…”