The longevity of SARS-CoV-2 antibodies and their cross-neutralization against variants of concern

The available coronavirus disease 2019 (COVID-19) vaccines generate neutralizing antibodies that target the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. While the short-term efficacy has been demonstrated, the long-term humoral response in the face of a rapidly mutating pathogen has yet to be characterized in detail. Similarly, individuals that have recovered from COVID-19 have expressed neutralizing antibody titers within a similar order of magnitude as those having received the vaccine. However, long-term immunity and cross-neutralization with newly emerging, more virulent lineages remain to be confirmed.

In a new study by researchers in the UK, the activity of neutralizing antibodies collected from the sera of individuals that contracted COVID-19 during the first wave of the pandemic is tested against variants of concern the B.1.1.7 (or UK) variant and the B.1.351 (or South African) variant, demonstrating somewhat reduced potency of neutralization towards these strains.

Study: Antibody longevity and cross-neutralizing activity following SARS–CoV–2 wave 1 and B.1.1.7 infections. Image Credit: Juan Gaertner / Shutterstock

The researchers – from King’s College, London, and the Guy’s and St Thomas’s NHS Foundation Trust – recently released their findings as a preprint on the medRxiv* server.

How long do neutralizing antibodies persist?

In a previously published paper, the authors studied the antibody response of SARS-CoV-2 infected individuals over a three-month period, observing peak sera neutralization activity around 4 weeks post-onset of symptoms, declining from here as antibody-secreting cells lower in population. In this work, sera were collected from the same individuals, where possible, as much as ten months post-infection. Additional samples were also collected from those that had contracted the B.1.1.7 strain 6 to 73 days earlier.

Sera was collected from 38 individuals that had caught COVID-19 during the first wave, 3 months post-infection, and then from the same individuals either 145-175 days post-infection (16 participants), 180-217 days post-infection (29 participants), or 257-305 days post-infection (19 participants). IgG and IgM against the SARS-Cov-2 spike protein were measured and found to decline at the later time points, particularly after six months post-infection, though was still detectable in some individuals.

The neutralizing activity of the collected sera towards HIV-1 based virus particles expressing the wildtype SARS-CoV-2 spike protein was also examined, being been seen previously to gradually decline over three months post-infection. This follow-up study reveals a slow in the rate of neutralization activity decline in the following 3 month period, with the highest percentage of samples exhibiting good neutralization at the peak (one month post-infection) being 48.2%, declining to 27.8%, around 3 months later, then 13.8% and 15.8% in the following months.

Individuals with the highest antibody titers often experience the most severe symptoms of COVID-19, and by correlating disease severity with antibody titer, the group supports this proposition. They also note that these individuals also tended to exhibit higher titers at the later time points, with less variation in magnitude of antibody response, compared with individuals with mild or asymptomatic COVID-19 that exhibited much greater variability in response intensity.

Cross-neutralization

Variants of concern B.1.1.7 and B.1.351 have demonstrated complete escape capacity against some monoclonal antibodies aimed at wildtype SARS-CoV-2. They have also shown improved resistance to neutralization by convalescent or vaccine sera collected at the peak of antibody response. Mutations to the spike protein are responsible not only for the increased transmissibility observed in these lineages, but also the improved escape capacity that has evolved by selective pressure.

Neutralization of wildtype, B.1.1.7, and B.1.351 pseudoviral particles was observed both by sera collected from individuals with wildtype COVID-19 10 months earlier, and by that collected from those more recently infected with the B.1.1.7 strain. At the early stages of antibody application, the B.1.351 strain demonstrated the greatest reduction in neutralization sensitivity compared to wildtype, though the difference was minimal at later stages post-infection. Importantly, infection with the B.1.1.7 strain generated antibodies that were effective against B.1.1.7 and wildtype, which were more similar to each other than those observed in sera during wave 1 of the pandemic.

Individuals experiencing severe symptoms from the B.1.1.7 strain, unlike those infected with the wildtype strain, displayed comparatively less enhanced neutralization capacity compared with mildly or asymptomatic individuals, which could be a result of improved immune evasion by the strain or a result of the increased administration of immunosuppressants in hospital settings.

*Important notice

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

Written by

Michael Greenwood

Michael graduated from Manchester Metropolitan University with a B.Sc. in Chemistry in 2014, where he majored in organic, inorganic, physical and analytical chemistry. He is currently completing a Ph.D. on the design and production of gold nanoparticles able to act as multimodal anticancer agents, being both drug delivery platforms and radiation dose enhancers.