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Studies assess antigen co-evolution of SARS-CoV-2 mutants

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In a recent study posted on bioRxiv* Preprint server, researchers analyzed antigen diversity across critical acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants such as the Omicron strain.

Studies: Omicron infection after vaccination induces broader immunity throughout the antigen space than prototype mRNA COVID-19 booster vaccination or primary infection.Image Credit: Corona Borealis / Shutterstockstudy: Omicron infection after vaccination induces broader immunity throughout the antigen space than prototype mRNA COVID-19 booster vaccination or primary infection..Image Credit: Corona Borealis / Shutterstock

Background

There are urgent requirements for coronavirus disease 2019 (COVID-19) vaccination technology to provide the broadest protection against current and future SARS-CoV-2 variants. SARS-CoV-2 causes more than 6.34 million deaths and 533 million infectious diseases worldwide.

Even if herd immunity continues to rise due to infectious diseases, primary series vaccinations, reinfections, or booster vaccinations, SARS-CoV-2 is still widespread worldwide. The SARS-CoV-2 vaccine is significantly immunized from severe COVID-19, but newly emerging viral variants such as Omicron continue to put them at risk. Effectiveness Even after booster vaccination.

About research

In this study, researchers evaluated antigenic variation in SARS-CoV-2 variants and analyzed neutralizing antibody responses to single and multiple exposures throughout the longitudinal infection and vaccination cohort.

The team used antigen mapping to use well-defined sera from the primary longitudinal group, such as Omicron BA.2.12.1, BA.4 / BA.5, and BA.2. Antigen heterogeneity across major SARS-CoV-2 variants was assessed in COVID-19 patients with a sequence-validated variant infection background. They used the sera of subjects infected with COVID-19 in the clinical features of epidemiological, immunological, and potentially pandemic emerging infectious disease (EPICC) studies. In fact, measurements of 1240 primary spontaneous neutralizing antibody levels were analyzed using antigen mapping to estimate the breadth of immunity between viral variants.

Equivalent assessments from an independent group of COVID-19 non-infected individuals before and after the second and third SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccination supplemented the initial analysis. Scientists have found that in a prospective assessment of the SARS-CoV-2 antibody positive conversion (PASS) study after two and three doses of the COVID-19 mRNA vaccine, the range of serum neutralization from 39 medical professionals. Was quantified. They then evaluated changes in immune dominance after infection and vaccination using antibody landscapes and other related methods for estimating antigen space.

result

Overall, researchers have found that the antigen map of pre-Omicron SARS-CoV-2 variants is consistent with the previously reported SARS-CoV-2 antigen map. Early SARS-CoV-2 mutants had strong clustering with common amino acid positions. This reasoning suggests that changes in specific amino acids regulate the antigen pattern.

The location of the Omicron BA.2 variant on the current map was consistent with the animal antigen model, but not with the map created using antisera from natural infections. The team also showed that the Omicron BA.4 / BA.5 and BA.2.12.1 variants are strongly linked to the beta cluster. This may shed light on the relevant epitopes.

Research results show that the immune predominant hierarchy varies between variants and can influence the choice of new vaccines. antigen.. Similarly, the delta mutant had the same antigen distance as the original strain after the third vaccination. On the contrary, Mu and Beta have moved closer to their ancestral virus sequences.

Antigen maps generated with neutralizing antibody titers from single antigen-exposed sera show that BA.1, BA.2, BA.2.12.1, and BA.4 / BA.5 are the most antigenic with other VOCs. Shows different. Antigen maps used A) serum collected after convalescent primary infection with different VOCs and B) serum titers from uninfected individuals who received 2 doses or C) 3 WT mRNA COVID-19 vaccines. Created using antigen mapping. The square sides of each grid correspond to the 2-fold dilution of the Pseudovirus Neutralization Assay. Antigen distance is measured in any direction on the grid. Antigens are indicated by circles and labeled. Serum is shown as a square and is colored by the infectious variant.  D) Neutralization fold difference in 95% confidence interval from ancestral strain to other variants on each map. For example, a 4-fold difference corresponds to a square in two grids on the antigen map.  E) Spikes and receptor binding domain substitutions for all mutants used in this study.

Antigen maps generated with neutralizing antibody titers from single antigen-exposed sera show that BA.1, BA.2, BA.2.12.1, and BA.4 / BA.5 are the most antigenic with other VOCs. Shows different. Antigen maps used A) serum collected after convalescent primary infection with different VOCs and B) serum titers from uninfected individuals who received 2 doses or C) 3 WT mRNA COVID-19 vaccines. Created using antigen mapping. The square sides of each grid are Pseudo virus Neutralization assay. Antigen distance is measured in any direction on the grid. Antigens are indicated by circles and labeled. Serum is shown as a square and is colored by the infectious variant. D) Neutralization fold difference in 95% confidence interval from ancestral strain to other variants on each map. For example, a 4-fold difference corresponds to a square in two grids on the antigen map. E) Spikes and receptor binding domain substitutions for all mutants used in this study.

The authors found that repeated exposure to the first SARS-CoV-2 strain induced by the mRNA vaccine expanded immunity to previously circulating Omicron variants after the third dose, providing a potent backboost. I found out what it means. In contrast to those who received only ancestral vaccinations, those who received Omicron’s post-vaccination infection (PVI) after two vaccinations showed a significantly flatter landscape and both variants. Shows broader protection for the body.

In addition, the team found that administration of Omicron PVI following three vaccinations elicited a stronger immune response than administration of only three vaccinations. This reasoning suggests that Omicron-based vaccines may help boost immunity in people who have been vaccinated for the third time, especially in ancestral strains.

The immunity of those who received a third vaccination followed by Omicron PVI, at least temporarily after vaccination, was comparable to those who received only two vaccinations and Omicron PVI. In particular, individuals who received two or three doses of cutin and Omicron PVI showed increased antibody width across a large number of mutants, including delta. The delta is located in a lower, farther region of the antigen map, indicating that Omicron PVI may have enhanced response to previous mutants.

In addition, by width gain plot analysis, all vaccinations and PVI cohorts were more BA.2.12.1 and BA.4 / than predicted based on antigen distances assessed along cone-based landscape ads. It became clear that the response to BA.5 was low. Antigen evaluation.

Conclusion

Research results have shown that over time, the antigen co-evolution of SARS-CoV-2 and its immune response in the host human population become more complex. The team will provide techniques to characterize the extent of the immune reflex to COVID-19 after exposure to various antigens.

Scientists have shown that Omicron PVI usually provides higher immunity than boost immunization with vaccines based on ancestral strains. Further exposure to the original and Omicron BA.1 antigens may extend the range of antibodies to BA.4 / BA.5. BA.4 was antigenically close to the ancestral strain, but the range obtained for BA.4 / BA.5 was lower than that for BA.1, suggesting a complex immune predominant tendency.

In order to develop a vaccination method for SARS-CoV-2 strains in the future, it is necessary to deeply understand the mechanism underlying these immune-dominant transitions and thoroughly evaluate the immune range. In addition, scientific discoveries on the development of antigenic heterogeneity of SARS-COV-2 are early antigenic by showing current trends in immune dominance and how sophisticated landscapes emerged. It may give insights into complex illnesses.

*Important Notices

bioRxiv Publish preliminary scientific reports that should not be considered definitive as they have not been peer-reviewed, guide clinical practice / health-related behaviors, and should not be treated as established information.

Journal reference:

  • Omicron infection after vaccination induces broader immunity throughout the antigen space than prototype mRNA COVID-19 booster vaccination or primary infection. Wei Wang, Sabrina Lusvarghi, Rahul Subramanian, Epsi Nusrat, Richard Wang, Emilie Goguet, Anthony Fries, Fernando Echegaray, Russell Vassell, Si’Ana Coggins, Stephanie Richard, David Lindholm, Katrin Mende, Evan Ewers, Derek La Colombo, Janet Joseph, Julia Rosman, Alfred Smith, Tahaniyat Larani, Catherine Version, Ryan Maves, Mirissa Jones, Rupal Modi, Nikil Fupliker, Jeffrey Ribazei, David Sanders, Carine Hollis Perry, Gregory Wang, Anurada Ganesan, Mark P Simons, Christopher Broder, David Tribble, Eric D. Laing, Brian Agan, Timothy H. Burgess, Edward Mitre, Simon Pollett, Leah C. Katzelnick, Carol D. Weiss. bioRxiv Preprint 2022, DOI: https://doi.org/10.1101/2022.07.05.498883, https://www.biorxiv.org/content/10.1101/2022.07.05.498883v1

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