Neutral antibodies develop within two weeks of SARS-CoV-2 infection, but their survival and intensity can vary according to each individual, raising concerns about the prospects for long-term immunity and effectiveness of COVID-19 vaccines.
In a PLOS ONE paper, published online February 11, 2021, researchers at the University of California San Diego School of Medicine report that an individual immune response to SARS-CoV-2, the virus that causes COVID, may -19, to be confined to the major histocompatibility complex or MHC, a set of variable genes encoding cell surface proteins essential for the immune system.
In particular, senior authors Maurizio Zanetti, MD, professor of medicine, Hannah Carter, PhD, professor of medicine and colleagues studied how the MHC interacts with two types of lymphocytes or immune cells called T and B.
The immune system responds to the attack of pathogens by releasing antibodies that aim to capture and neutralize the pathogen. The production of antibodies against proteins requires a productive cooperation between the T lymphocyte and the B lymphocyte, which requires both adjacent antigen sequences to be initiated by the MHC on B cells. involved both cells favorably and non-randomly. The MHC serves as the link between the T and B lymphocytes in this process. “
Maurizio Zanetti, MD, Professor of Medicine, University of California San Diego
Based on this reasoning, the researchers performed a computer analysis of all possible fragments of the RBM protein spike, which is a stimulant for the human immune response and for vaccine activity, the co link to the more than 5,000 different MHC molecules represented in the global human population.
To their surprise, the authors found that the mean MHC bias for exhibiting RBD-based peptides is low. Since MHC binding is an indirect measure of the likelihood that the T cell will be activated and the B lymphocyte will be stimulated to produce antibodies against the RBM, the authors stated that it continues to the production of specific RBM antibodies could be inhibited by poorly modulating these concentrations of the virus to the MHC.
“This could then lead to neutral neutral reactions of antibody,” said first author Andrea Castro, a member of Carter’s lab. “And with respect to SARS-CoV-2, poor expression of major RBD components with many MHC alleles may act as a barrier to the production of neutral antibodies targeting the RBM.”
The scientists suggest that individuals’ immunological history may play a role in T cell response and subsequent activation of B lymphocytes that can produce targeted neutral antibodies.
The study has two effects, Carter said.
“One is that the ability to generate antibodies with strong neutral activity could vary greatly from individual to individual within the general population, reflecting the great genetic diversity of the MHC. the other is that lack of effective cooperation between T and B lymphocytes may affect the longevity of neutralizing antibody responses in infected individuals. “
The authors note that multiple studies have reported that the neutralization of antibodies in infectious individuals (hospitalized patients, health care workers, and individuals) falls within three months.
“To these considerations, one could add to the impact of the recent mutations in the RBM, such as those in the UK, South Africa and Brazilian of the virus, “Zanetti said. The topology of the mutations in these new variables is indicative of a possible further breakdown of the immunological relay between T and B lymphocytes, with additional adverse effects on the ability of individuals in the global population to generate high-quality and long-term neutral antibody responses against SARS-CoV-2. “
Source:
University of California San Diego
Magazine Reference:
Castro, A., et al. (2021) In a silico study suggesting less effective MHC-II expression of SARS-CoV-2 RBM peptides: Effect for neutralizing antibody responses. PLOS AON. doi.org/10.1371/journal.pone.0246731.