Cracking the genetic code for COVID-19 vaccine effectiveness

Researchers have uncovered critical insights into how our genetic makeup affects the body’s response to COVID-19 vaccines. The study, published in Nature Communicationsmay open new paths to personalized vaccination strategies.

The study, led by Junqing Xie, Postdoctoral Researcher in Pharmacoepidemiology and Pharmacogenetics at NDORMS, examined genetic variations in human leukocyte antigen (HLA) genes and their impact on antibody responses induced by vaccination against COVID-19.

HLA genes play a crucial role in the immune system’s ability to recognize and respond to foreign substances, including viruses, and have been shown to be effective in response to other vaccines such as hepatitis B, measles and influenza.

The researchers analyzed data from over 368,000 participants who had received a vaccine against COVID-19, with a subset of 194,371 individuals having their antibody levels measured. The study confirmed findings from previous studies that certain genetic variations, particularly in the HLA-DQB1*06 gene, are associated with improved antibody responses to COVID-19 vaccines.

However, the team found that while the DQB1*06 variant increases antibody production, it does not support the claim that this alone can significantly reduce the risk of COVID-19 in the general population. This shows that antibody levels alone do not tell the full story when it comes to vaccine effectiveness.

“Our findings highlight the complex interplay between genetics, antibody responses, and real-world protection against COVID-19,” Junqing explained. “It’s not as simple as just raising antibodies—we have to consider the scope and the broader immune mechanisms at play.”

The researchers discovered and validated six additional HLA alleles that independently affect antibody responses. Importantly, they also found that the combined effect of these HLA variations may affect the risk of spreading COVID-19 infections.

The team also used those genetic variations to randomize antibodies induced by the COVID-19 vaccine (a new statistical method) and estimated that antibody positivity provides about 20% protection against infection and 50% protection against severe disease. This underscores the importance of other immune factors, such as T cells, in providing comprehensive protection against the virus.

“This is an important advance in our understanding of the genetic factors that shape the body’s response to COVID-19 vaccines,” said Daniel Prieto Alhambra, corresponding author for the study. “By discovering these new genetic associations, we are one step closer to developing personalized vaccination strategies that can optimize protection for individuals.”