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
Mucosal linings in the eyes, nose, mouth, and throat act as the first line of defense against invading respiratory pathogens, such as 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. In 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 compared to infection-naïve individuals.
In the current study, scientists compare plasma and mucosal antibody levels from saliva and tear samples, respectively. The ability of these antibodies to induce Fc effector functions and cross-react with SARS-CoV-2 variants among Vaxzevria-vaccinated individuals with or without prior SARS-CoV-2 infection was also determined. Furthermore, the researchers evaluated how viral exposure impacts mucosal antibody responses after Vaxzevria vaccination.
COVID-19-recovered individuals exhibited IgG responses in both saliva and plasma samples after a single dose of the Vaxzevria vaccine as compared to infection-naïve individuals who received two vaccine doses. Moreover, COVID-19-recovered individuals exhibited significantly higher spike-specific engagements of Fc-receptors and spike-specific salivary IgA1 responses after the first vaccine dose.
The salivary and plasma antibody response and Fc receptor engagement in COVID-19-recovered individuals after the second vaccination failed to reach the levels observed two weeks after the first vaccine dose. However, 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 first and second vaccinations. However, these individuals exhibited significant induction in plasma IgG and Fc engagement responses after receiving a third 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 need for booster doses capable of inducing robust anti-SARS-CoV-2 mucosal immunity.
Neutralizing antibody response at mucosa
The virus neutralization assay findings revealed that both the first and second COVID-19 vaccinations could not induce a sufficient salivary neutralizing response in most 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 range of SARS-CoV-2 VOCs after vaccination. However, this response was primarily targeted against the wild-type SARS-CoV-2 strain, with weaker recognition of more recent Omicron variants.
Salivary IgAs, rather than plasma IgA, were cross-reactive across a broad range of SARS-CoV-2 VOCs in COVID-19-recovered individuals, particularly after the first vaccination. Thus, the induction of cross-reactive IgA at the mucosa is crucial for developing protection against newly emerging viral variants.
Interestingly, our findings show that IgG antibodies in the bloodstream can mostly recognize the original virus, while mucosal IgA antibodies is able to target both the ancestral virus and the newer variants.”
Intramuscularly-delivered Vaxzevria vaccine can effectively induce both systemic and mucosal antibody responses in COVID-19-recovered individuals. Moreover, 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, as a result, do not 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 may be necessary to improve localized antibody protection at the mucosal surfaces.”
- 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