The coronavirus disease 2019 (COVID-19) pandemic, caused by the rapid spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has claimed more than 6.9 million lives worldwide.
Study: Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination. Image Credit: Yurchanka Siarhei/Shutterstock.com
Several SARS-CoV-2 variants have emerged due to genomic mutations of the ancestral or wild-type (WT) SARS-CoV-2 strain. Among these variants, those classified as variants of concern (VOCs) pose a greater challenge to vaccine- and/or infection-induced long-term immunity.
Many COVID-19 vaccines have been developed targeting the spike protein of the SARS-CoV-2 WT strain. Hence, it is important to assess the efficacy of these vaccines against the new SARS-CoV-2 strains, particularly VOCs.
Background
Most recently, the SARS-CoV-2 Omicron variant has been circulating in the majority of countries across the world. Since the emergence of VOCs, the Omicron variant was found to be the most antigenically distinct strain.
Most mutations of this strain affect the S1 subdomain of the spike protein, which aids various degrees of immune escape and a significant decrease in long-term protection against reinfection.
Even though many studies have indicated the reduction in the neutralizing capacity of antibodies induced by earlier variants or vaccination, not many documents regarding the avidity of persisting antibodies are available. Antibody avidity describes the binding strength to the target antigen, which is extremely important for antibody functionality.
Prior studies have shown that avidity increases over time after contact through B cell maturation at germinal centers. This implies the possibility of offsetting the waning effect of antibodies to a certain level.
A recent Frontiers in Immunology study characterized the concentration and binding affinity of antibodies induced by SARS-CoV-2 WT strain against the Omicron subvariant BA.1 (OM).
About the study
A post-infection cohort that included seropositive adult participants of the Ischgl-2 seroprevalence study was developed. This cohort included participants who contracted SARS-CoV-2 infection during the first infection wave in March/April 2020. Blood samples of the participants were collected in November 2020, i.e., 7 to 8 months after pathogen contact. None of the participants reported a second infection during blood collection (sampling).
This cohort also included ShieldVacc-2 study participants, who received their second dose of the COVID-19 vaccine (BioNTech/Pfitzer) in March/April 2021. For these participants, blood samples were collected in November 2021, i.e., 7 to 8 months after antigen contact.
A total of 690 age- and sex-matched participants were recruited, among which 354 received double mRNA–vaccine and 336 were WT-infected. Both groups had a higher number of male participants.
Study findings
Consistent with previous studies, the current study revealed that WT infection–generated antibodies have a lower binding and neutralizing antibody titer toward the OM epitopes. Even though the reduced concentration of antibodies against the mutated antigen was expected, an unwarranted antibody avidity to the Omicron variant was found to be not only non-inferior to WT avidity. Interestingly, the binding affinity was found to be marginally higher towards OM antigen across all participants of the cohort.
Notably, this study indicated that pre-existing non-neutralizing antibodies and antibody avidity have a protective role against severe infection. This factor might have prevented the severity of the Omicron era. In the future, researchers must elucidate whether any mutation-associated structural change of epitopes has led to the aforementioned observation.
Analysis of the blood samples indicated a significant decline in IgG antibodies after an initial peak within the first three months after antigen contact. This observation was particularly true for vaccinated participants. After the initial surge, the antibody titers declined and plateaued to a stable level, and this concentration persisted for at least one year.
Prior studies have indicated the possibility of structural changes after mutations, which could affect the functionality and binding capacity of antibodies. However, the current study indicated a reduced but significant preservation of binding capacity against the mutated variant both in the convalescent and vaccinated groups. Compared to the WT-infected group, the vaccinated group exhibited higher antibody titers against the OM.
The concentration-matched avidity testing adopted in this study offered a better comparability of the binding affinity due to the fact that avidity maturation is a time-dependent process.
Strengths and limitations
A key strength of this study is its large sample size and comparability of sex and age distribution across the two groups, i.e., WT infected and vaccinated. In addition, this study used the ELISA assays validated based on European standards.
Even though prior infection in the vaccinated cohort was excluded based on participants' infection history, there is a possibility of a residual risk of past infections that might impact results. The use of the Omicron subvariant (BA.1) limited the generalizability of the study.
The current study focussed on humoral aspects of immunity and failed to consider cellular immunity due to the lack of relevant data. Future research must analyze the synergistic effect of both types of immunities on SARS-CoV-2 disease outcomes.
Despite the limitations, this study revealed the presence of a non-negligible proportion of binding antibodies in the study cohort that is effective against the Omicron BA.1 variant.
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