Fri. Jan 21st, 2022

Researchers from the United States have conducted a study of coronavirus disease 19 (COVID-19) convalescent patients (CP) and post-vaccinated (PV) population to identify the minimum levels of antibody required to protect against severe acute respiratory syndrome coronavirus 2 (SARS) -CoV-2) infection.

Study: Protective properties of COVID-19 convalescent and post-vaccination IgG antibodies.  Image credit: ktsdesign / ShutterstockStudy: Protective properties of COVID-19 convalescent and post-vaccination IgG antibodies. Image credit: ktsdesign / Shutterstock

Quantification of the levels of protective antibodies in post-vaccinated individuals is essential to monitor the degradation of protective immunity after vaccination and relate it to the incidence of breakthrough infections.

A pre-printed version of the research paper is available at medRxiv* server while the article is undergoing peer review.

Background

The spike glycoprotein (SP) forms the protruding spikes on SARS-CoV-2 that mediate attachment of the spherical virions to the host cells and subsequent fusion with epithelial cell membranes, facilitating penetration and infection. It is a homotrimer consisting of two subunits, S1 and S2, of which the S1 protein interacts with the angiotensin-converting enzyme-2 (ACE-2) receptor on the cell surface through the receptor binding domain (RBD), while S2 protein mediates cell membrane fusion.

RBD is the target for 90% of the neutralizing antibodies that constitute the critical element in the protective immune response against the virus. The two mRNA COVID-19 vaccines developed by Pfizer and Moderna are specifically designed to generate antibodies against RBD.

Although several studies have focused on characterizing the antibody response to SARS-CoV-2, the studies defining the actual antibody concentrations and target binding affinities in CP and PV populations have been largely lacking.

What did the researchers do?

The team quantified the antibody concentrations and antibody binding affinities for both SP and RBD in convalescent plasma samples as well as plasma samples obtained from individuals who completed the two mRNA vaccination protocols (Pfizer and Moderna), using quantitative ELISA methodology.

Knowing the protective effect of these vaccines through Phase Three clinical trial reports, the team estimated the protective immunoglobulin (IgG) anti-SP antibody levels and analogous values ​​for two indices that combined antibody concentrations and binding affinities for both SP and RBD.

What did the researchers find out?

For the convalescent plasma population (n = 21), anti-SP IgG antibody levels ranged from 33.1 µg / ml to 1.6 mg / ml (geometric mean [GM] 190 /g / ml), while the corresponding values ​​for the post-vaccination plasma population (n = 21) ranged from 4.9 µg / ml to 1.5 mg / ml (GM 176 µg / ml). The measurement of anti-SP IgG antibodies for the whole nail protein was greater in the convalescent patient population, possibly reflecting that the mRNA vaccines produce antibodies more specific for RBD. Both sample populations were similar in protective antibody level of 7.5 μg / ml was determined based on 95 of the normal distribution of the post-vaccination population.

A recent meta-analysis of neutralization data from seven vaccine studies reported that 50 protection against detectable SARS-CoV-2 infection would be provided by 20.2 of the geometric mean convalescence level of neutralizing antibody, corresponding to 2.9 Igg IgG anti-SP / ml. This is consistent with the value of 7.5 µg / ml responsible for 95 protection observed in this study.

SP binding affinities (KD) of convalescent plasma samples ranged from 0.1 to 2.2 nM (mean = 0.87 ± 0.47 nM), while the range of RBD binding affinities was much narrower, all being subnanomolar (mean = 0 , 49 ± 0.15 nM). Spike protein binding affinities of post-vaccination plasma IgG antibodies were relatively broader (0.2-3.9; 1.95 ± 0.99 nM) than for the convalescent antibody populations. However, the post-vaccination anti-RBD affinities were virtually the same (0.48 ± 0.34 nM; p = 0.877).

Measuring antibody binding affinity adds value to assess the robustness of the antibody response, leading to the conclusion in this study that naturally acquired immunity after SARS-CoV-2 infection is comparable to vaccine-induced immunity, ”the team emphasizes.

Implications

Information on antibody concentrations and target affinities allows a practical understanding of protective immune mechanisms.

For example, based on a SARS-CoV-2 diameter of 100 nm and peak protein surface density of 25 trimers per virion, a concentration of 7.5 µg anti-SP IgG / ml would give 12 molecules of antibody per tip protein molecule in a viral saturation of a mucosal surface 10 µm in depth. With SP binding affinity (KD) of 1.0 nM, 95 SP molecules will be bound by the antibody. With the mean binding affinity of 0.48 nM found for anti-RBD IgG in fully vaccinated individuals, 99 SP molecules would be bound by the antibody. This calculation provides a conceptual framework in accordance with the empirical data reported here and the basis for developing a true protective index based on the study of plasma.

These measures will also allow for a realistic assessment of immune evasion of viral variants through monitoring of the rate of decreasing protective antibody.

*Important message

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered essential, guide clinical practice / health-related behavior or be treated as established information.

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