This is a summary, written by members of the CITF Secretariat, of:
Norton NJ, Ings DP, Fifield KE, Barnes DA, Barnable KA, Harnum DOA, Holder KA, Russell RS, Grant MD. Characteristics of vaccine- and infection-induced systemic IgA anti-SARS-CoV-2 spike responses. Vaccines (Basel). 2023 Sep 7;11(9):1462. doi: https://doi.org/10.3390/vaccines11091462.
The results and/or conclusions contained in the research do not necessarily reflect the views of all CITF members.
A CITF-funded study, published in Vaccines, showed that vaccination with an original COVID-19 mRNA vaccine induces a stronger circulating IgA immune response to the wildtype SARS-CoV-2 strain than to the Omicron strains. Participants vaccinated three or four times had significantly stronger anti-full-length spike (FLS) IgA responses against wildtype than against Omicron BA.1. The levels of IgA responses remained higher against the wildtype FLS, even after an Omicron breakthrough infection following two or three vaccine doses. This study was led by Dr. Michael Grant (Memorial University of Newfoundland).
- Two intramuscular vaccinations with the original SARS-CoV-2 mRNA-based vaccines induced systemic SARS-CoV-2 anti-full- length spike (FLS) IgA against the wildtype strain. A third vaccine dose boosted this response, but levels were significantly lower after a fourth vaccine dose.
- Participants experiencing Omicron breakthrough infections after two or three vaccines had higher levels of circulating anti-SARS-CoV-2 spike IgA than participants with a fourth vaccine dose but no Omicron breakthrough infection.
- Participants with higher levels of vaccine-induced systemic SARS-CoV-2 spike or receptor binding domain (RBD) IgA (after three vaccine doses) had a reduced risk of an Omicron breakthrough infection.
- Participants with two or three vaccine doses and an Omicron breakthrough infection developed higher circulating SARS-CoV-2 spike IgA levels against the wildtype and Omicron BA.1 strain that remained elevated for over 150 days.
- Participants vaccinated three or four times with vaccines based on the wildtype spike protein had significantly stronger anti-FLS IgA responses against wildtype than against Omicron BA.1. The levels of IgA responses were higher against the wildtype FLS even after an Omicron breakthrough infection following two or three vaccine doses.
- Participants vaccinated with three vaccines, four vaccines, two vaccines followed by an Omicron infection, and three vaccines followed by an Omicron infection had greater circulating IgG levels against wildtype FLS than Omicron BA.1 FLS.
These findings reveal that vaccination with an ancestral SARS-CoV-2 antigen imposed immunological imprinting on IgA responses, with preferred recognition of ancestral versus Omicron S protein, even after Omicron breakthrough infection. This supports the idea of offering Canadians monovalent vaccines that address currently circulating variants in Canada.
The authors suggest that it is important to investigate the relationship between circulating and mucosal IgA antibodies to determine their significance in protecting against respiratory infections, including SARS-CoV-2. Understanding the dynamics of IgA responses and their role in immunity can help improve vaccine strategies and preparedness for emerging virus variants.
This study included participants from an ongoing research cohort at Memorial University of Newfoundland and Labrador, and they were selected based on prior suspicion of SARS-CoV-2 infection or confirmation with reverse-transcriptase polymerase chain reaction (RT-PCR). Individuals who self-reported Omicron infections—between February and August 2022—based on RT-PCR or rapid test results, following receipt of at least two Health-Canada-approved anti-SARS-CoV-2 vaccines against the wildtype strain, were included.