In the body's mucous membranes, such as those in the respiratory and digestive tracts, Y-shaped soldiers stand guard—these are Immunoglobulin A (IgA), the first line of defence against invading pathogens like bacteria and viruses.
“Studies on other respiratory viruses, such as influenza and RSV, have shown that IgA plays a crucial role in limiting infection and transmission of these viruses at mucosal surfaces,” explained Laurent Rénia, a Senior Fellow and Principal Investigator at A*STAR Infectious Diseases Labs (ID Labs).
However, much remains uncertain about how the human immune system responds to SARS-CoV-2 variants such as Omicron, especially post-vaccination. This uncertainty complicates the design of effective strategies to shield against viral variants. Most studies have focused on the IgG isotype, said Rénia, largely because these antibodies are more abundant in the body and easier to measure using standard blood tests.
Rénia worked with a multidisciplinary team from ID Labs, A*STAR’s Singapore Immunology Network (SIgN) and Bioinformatics Institute (BII); and Singapore’s National Centre for Infectious Diseases, Ng Teng Fong General Hospital, Alexandra Hospital, National University Polyclinic, National University Hospital and Nanyang Technological University; to investigate IgA’s role in protecting against SARS-CoV-2 variants, with the aim of advancing vaccine development.
In their study, Rénia and Yun Shan Goh, a Senior Research Scientist at ID Labs, led the examination of two cohorts of Singaporean participants who received mRNA COVID-19 vaccines and booster shots. Using a patented a specialised antibody assay that differs from conventional lab tests by uniquely detecting both IgG and IgA, the team measured the levels of variant-specific IgA and IgG antibodies in these individuals and monitored their infection status over 8 to 12 months.
They observed that individuals who remained uninfected during the follow-up period had higher levels of variant-specific IgA antibodies shortly after receiving their booster shots compared to those who became infected. This suggests that IgA, more than IgG, may contribute to protection against the Omicron variant.
These findings also indicate that vaccines designed to specifically enhance IgA responses, especially at mucosal surfaces, may offer better protection against SARS-CoV-2 and its variants. “It may be possible to identify the low IgA responders and have more targeted booster vaccination to better protect these individuals from infection,” commented Goh.
Goh suggested that this might involve developing intranasal vaccines aimed at boosting IgA levels at the virus's entry points, potentially providing more effective protection against infections.
Speaking on the team’s next steps, Goh said: “We are investigating the mechanisms by which IgA mediates its protective functions and how IgA responses evolve over time in response to vaccination.”
The A*STAR-affiliated researchers contributing to this research are from the A*STAR Infectious Diseases Labs (ID Labs), Singapore Immunology Network (SIgN) and Bioinformatics Institute (BII).
