In a recent study published in Immunology & Cell Biology, scientists examine the protective efficacy of coronavirus disease 2019 (COVID-19) vaccine-induced mucosal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs).

Study: Mucosal antibody responses following Vaxzevria vaccination. Image Credit: ANDRES MENA PHOTOS / Shutterstock.com

Background

Mucosal linings within the eyes, nose, mouth, and throat act as the primary line of defense against invading respiratory pathogens, akin to SARS-CoV-2. Previous studies have indicated that SARS-CoV-2 spike protein-specific mucosal immunoglobulin A (IgA) antibodies can provide strong protection against breakthrough COVID-19 infections and novel viral variants.

Intramuscularly-administered adenoviral vector-based COVID-19 vaccines have been shown to induce weak mucosal immune responses in infection-naïve individuals. On this context, a recent study reported that the adenoviral vector-based COVID-19 vaccine Vaxzevria induces higher levels of mucosal IgG and IgA antibodies in COVID-19-recovered individuals in comparison with infection-naïve individuals.

In the present study, scientists compare plasma and mucosal antibody levels from saliva and tear samples, respectively. The power of those antibodies to induce Fc effector functions and cross-react with SARS-CoV-2 variants amongst Vaxzevria-vaccinated individuals with or without prior SARS-CoV-2 infection was also determined. Moreover, the researchers evaluated how viral exposure impacts mucosal antibody responses after Vaxzevria vaccination.

Necessary observations

COVID-19-recovered individuals exhibited IgG responses in each saliva and plasma samples after a single dose of the Vaxzevria vaccine as in comparison with infection-naïve individuals who received two vaccine doses. Furthermore, COVID-19-recovered individuals exhibited significantly higher spike-specific engagements of Fc-receptors and spike-specific salivary IgA1 responses after the primary vaccine dose.    

The salivary and plasma antibody response and Fc receptor engagement in COVID-19-recovered individuals after the second vaccination failed to succeed in the degrees observed two weeks after the primary vaccine dose. Nevertheless, the antibody levels and Fc receptor engagement in saliva after the second vaccine dose remained significantly higher than the pre-vaccination responses against SARS-CoV-2 VOC spike antigens.

Unlike vaccinated COVID-19-recovered individuals, infection-naïve vaccinated individuals exhibited weak salivary and plasma antibody responses after the primary and second vaccinations. Nevertheless, these individuals exhibited significant induction in plasma IgG and Fc engagement responses after receiving a 3rd booster dose of a messenger ribonucleic acid (mRNA) COVID-19 vaccine. Nevertheless, this booster dose caused only modest changes in salivary antibody response in these individuals.

Overall, these findings indicate that salivary IgA and antibody-mediated Fc receptor engagement responses decline after a second vaccine dose in COVID-19-recovered individuals. This highlights the necessity for booster doses able to inducing robust anti-SARS-CoV-2 mucosal immunity.

Neutralizing antibody response at mucosa

The virus neutralization assay findings revealed that each the primary and second COVID-19 vaccinations couldn’t induce a sufficient salivary neutralizing response in many of the COVID-19-recovered individuals.

In contrast, COVID-19 recovered and infection-naïve individuals exhibited broad neutralizing responses in plasma against SARS-CoV-2 VOCs after first and booster vaccination, respectively.

COVID-19-recovered individuals exhibited mucosal antibody-mediated Fc receptor engagement responses against a wide selection of SARS-CoV-2 VOCs after vaccination. Nevertheless, this response was primarily targeted against the wild-type SARS-CoV-2 strain, with weaker recognition of newer Omicron variants.

Salivary IgAs, quite than plasma IgA, were cross-reactive across a broad range of SARS-CoV-2 VOCs in COVID-19-recovered individuals, particularly after the primary vaccination. Thus, the induction of cross-reactive IgA on the mucosa is crucial for developing protection against newly emerging viral variants.

Interestingly, our findings show that IgG antibodies within the bloodstream can mostly recognize the unique virus, while mucosal IgA antibodies is in a position to goal each the ancestral virus and the newer variants.”

Study significance

Intramuscularly-delivered Vaxzevria vaccine can effectively induce each systemic and mucosal antibody responses in COVID-19-recovered individuals. Furthermore, the study findings indicate that IgG-mediated mucosal responses are largely non-neutralizing and specific to the wild-type strain of SARS-CoV-2 and, in consequence, don’t provide sufficient protection against breakthrough infections. In contrast, vaccine-induced, highly cross-reactive mucosal IgA response can effectively provide protection against newly emerging viral variants.  

These results indicate that previous exposure to SARS-CoV-2 through the mucosal route could also be crucial to enhance localized antibody protection on the mucosal surfaces.”   

Journal reference:

• Selva, K. J., Ramanathan, P., Haycroft, E. R., et al. (2023). Mucosal antibody responses following Vaxzevria vaccination. Immunology & Cell Biology. doi:10.1111/imcb.12685