Understanding the Effects of the mRNA Vaccine

A very interesting paper from Dr. Mark Davis’ group shows that in response to the mRNA vaccine, CD8 T cell responses are attenuated in people who had prior COVID compared to uninfected people. What does this mean? (1/)https://t.co/thiEOpgUA9

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Fei Gao, @VMallajosyula et al used SARS-CoV-2 pMHC-spheromers to detect viral antigen-specific CD8 and CD4 T cells from people who were vaccinated, infected or both. Spheromers are peptide-MHC multimers (12 units) that are more sensitive than conventional pMHC tetramers. (2/) pic.twitter.com/WckDq7dNen

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

CD8 T cell responses to viral antigens were compared in people who received the mRNA vaccines to those with prior infection with SARS-CoV-2. The vaccine induced significantly better CD8 T cell immunity in both quantity and quality than the infection. (3/) pic.twitter.com/WmOgPcEn8d

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Notably, people who recovered from COVID and then were vaccinated had much lower CD8 T cell response than people who were not infected (naive) and vaccinated. The CD8 T cells’ ability to secrete cytokines and become activated was also poorer in the recovered group. (4/) pic.twitter.com/kjuNjTzkkM

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Why does infection induce poorer CD8 T cell immunity than the vaccine? The answer may be related to the ability of this virus to impair MHC I presentation (5/)https://t.co/IRZBcAU8T7https://t.co/HXszC6dUIghttps://t.co/96Y73jTSFfhttps://t.co/lwTqLZVe5K

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Why does prior infection impair CD8 T cell responses induced by the mRNA vaccine? This may imply induction of some form of regulatory immune response by the infection, or sequestration of Spike by preexisting antibodies for MHC I presentation. (6/)

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Does this mean that prior infection with COVID will render people susceptible to future reinfections? Not necessarily. We know that prior infection promotes better neutralizing antibody responses after vaccination - the best correlate of protection. (7/)https://t.co/0gvlaZHorJ pic.twitter.com/C8oRb7J2zS

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Does the study by Gao et al mean that prior COVID will make people immunodeficient (unable to fight any infection)? Not likely based on other data. @JohngLab found enhanced (not lower) immunity to flu vaccine in men who recovered from mild COVID. (8/)https://t.co/3ZtUmpJyoq

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023

Could impaired CD8 T cell immunity lead to long COVID? Possibly - by enabling the SARS-CoV-2 infection to persist or by enabling reinfections to be more productive. But this hypothesis must be tested. A great paper with much to think about. (End)

— Prof. Akiko Iwasaki (@VirusesImmunity) March 21, 2023