Prior vaccination enhances immune response during SARS-CoV-2 breakthrough infection

In a recent study posted on Bio Rxiv* Using a preprint server, researchers can track previous coronavirus disease 2019 (COVID-19) vaccination against immune responses during breakthrough infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Evaluate the impact.

study: Prior vaccination enhances the immune response during SARS-CoV-2 breakthrough infection, resulting in early activation of memory T cells and subsequent production of potent neutralizing antibodies. Image Credit: Lightspring / Shutterstock.com

How effective is the COVID-19 vaccine?

In early 2021, there was a significant shift in the trajectory of the pandemic with a significant increase in COVID-19 vaccination coverage. Nonetheless, the protection conferred by vaccine-induced antibodies was found to wane several months after vaccination.

Additional messenger ribonucleic acid (mRNA) vaccine doses were subsequently approved to increase antibody titers and provide more protection against symptomatic disease. Although spike-specific T cells may proliferate and activate memory CD8 T cells during breakthrough infection, the dynamics of memory B and T cell activation associated with antibody generation remain unclear.

About research

In this study, investigators assess the kinetics of SARS-CoV-2 spike-specific cellular and humoral recall responses in response to SARS-CoV-2 breakthrough infection in vaccinated individuals.

To determine the dynamics of recall responses primed by vaccination during SARS-CoV-2 breakthrough infection, patients who received at least three mRNA COVID-19 vaccine doses and were infected with SARS-CoV-2 in 2022 Blood samples were collected from individuals who reported subsequent infection. The Omicron variant and its subvariants were the predominant circulating strains in the United States.

To elucidate whether Omicron’s breakthrough infection led to antibody responses specifically targeting its variant strains, Neutralizing antibody compared to targeting the SARS-CoV-2 D614G strain.

A panel of protein tetramer probes was utilized to investigate plasmablast responses during SARS-CoV-2 breakthrough infection.These probes helped evaluate the antigen– Peripheral blood-derived B-cell reactivity, including those targeting the SARS-CoV-2 spike and nucleocapsid proteins, as well as the spike domain containing spike-2 (S2), N-terminal domain (NTD), and receptor Binding domain (RBD) and RBD variants from BA.1, BA.4/5, and Delta.

Investigation result

RBD-binding antibodies were detected in all patients before SARS-CoV-2 breakthrough infection. However, antibody titers were nearly 5-fold lower than the peak titers reported 2 weeks after his third mRNA vaccination.

During breakthrough infection, RBD-binding antibody titers remained stable during the first week and then doubled between days 7 and 15. Antibody binding titers against Omicron and D614G spike RBD increased to a similar extent, indicating that Omicron infection was induced. Generation of circulating antibodies that continue to bind wild-type strains and new virus variants.

Similar results were obtained for neutralizing antibody titers against the wild-type D614G strain of SARS-CoV-2. spike proteinBy day 15, booster vaccination significantly increased D614G neutralizing antibody titers by almost 8-fold.

However, during breakthrough infection, D614G neutralizing antibody levels did not rise during the first week, increased 2.4-fold by day 15 post-infection, and rose slightly further at day 45. .

Similarly, during the first week of breakthrough infection, there was no quantifiable increase in neutralizing titers in response to the Omicron BA.1.1 subvariant. By week 2, BA.1.1 neutralizing antibodies rose more rapidly than his D614G and continued to increase 7.8-fold on day 15.

The neutralizing potency of BA.1.1 antibody responses compared to D614G dramatically increased from less than 25% pre-infection to 50% by day 15. This neutralization ratio did not change over his first week of breakthrough infection.

The team noted that the absolute boost in neutralizing antibodies was the same for both variants, even though the fold change reported for BA.1.1 neutralizing antibodies was greater than for D614G. Thus, antibodies generated in response to breakthrough infection may effectively neutralize both BA.1.1 and D614G. Nevertheless, preferential production of BA.1.1 neutralizing antibodies resulted in a considerable increase in neutralizing potency.

During the first week of breakthrough infection, the frequency of B cells detecting the full-length spike protein or specific spike domains remained constant. Nucleocapsid-specific memory B cells were virtually undetectable in most patients at the first time point of infection.

Nucleocapsid- and spike-specific memory B cells increased throughout the second week of infection, whereas the frequency of nucleocapsid-specific memory B cells was nearly 80-fold lower by day 15.

Among spike protein-specific memory B cells, S2-specific B cells did not increase appreciably during breakthrough infection. By comparison, the frequency of B cells binding NTD and RBD increased significantly by day 1, including B cells interacting with BA.1 and BA.5 RBD.

Conclusion

Prior vaccination produced a tailored SARS-CoV-2 spike-specific recall response compared with uninfected individuals. This was characterized by increased neutralizing antibodies and activation of memory B cell levels. The current study highlights the importance of memory B and T cells during recall immune responses in patients with moderately symptomatic breakthrough infections and sheds more light on the mechanisms responsible for vaccine-induced immunity.

*Important Notices

Bio Rxiv We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.