PrePrint: SARS-CoV-2 501Y.V2 Escapes Neutralization by South African COVID-19 Donor Plasma

 

#15,729

The big pandemic news over the past 5 weeks has been the detection of multiple, rapidly spreading COVID-19 variants that have recently emerged in the UK, South Africa, Brazil, and most recently, the United States. 

Variants, caused by accrued mutations within the virus, are normal and to be expected.  And most have no discernable impact on the way the virus behaves.  Thus far hundreds of variants have been detected, and only a handful appear to provide a biological advantage to the virus. 

But in the UK, the B.1.1.7 variant has become dominant in just a matter of weeks, due to its enhanced transmissibility.  Another variant, which was first detected in South Africa (501Y.V2), not only appears more transmissible, it has previously been linked to reduced antibody recognition, which is feared might reduce vaccine effectiveness or increase reinfection rates. 

The P.1. variant in Brazil, while different, shares the E484K mutation with the South African variant, which may also result in reduced antibody recognition. As for the rest, we are just starting to learn about them. 

Yesterday another Preprint study appeared online, this time testing the South African variant against 3 classes of monoclonal antibody therapies, and convalescent plasma collected from recovered COVID patients.  The goal was to determine if these treatments would be effective. 

While this is just one study - and the data should be interpreted with caution - the results suggest that some of these new variants likely present a greater reinfection risk and they may not respond to some therapeutics. 

As for the $64 question; whether - or how well -  current vaccines will protect against them, that remains an important, but unanswered question.

We've the link and abstract to the paper, plus some excerpts from the discussion, followed by some expert reaction from the Science Media Centre.  

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

Constantinos Kurt Wibmer, Frances Ayres, Tandile Hermanus, Mashudu Madzivhandila, Prudence Kgagudi, Bronwen E Lambson, Marion Vermeulen, Karin van den Berg, Theresa Rossouw, Michael Boswell,  Veronica Ueckermann,  Susan Meiring,  Anne von Gottberg,  Cheryl Cohen, Lynn Morris,Jinal N Bhiman, Penny L Moore

doi: https://doi.org/10.1101/2021.01.18.427166

This article is a preprint and has not been certified by peer review [what does this mean?].

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Abstract

SARS-CoV-2 501Y.V2, a novel lineage of the coronavirus causing COVID-19, contains multiple mutations within two immunodominant domains of the spike protein. Here we show that this lineage exhibits complete escape from three classes of therapeutically relevant monoclonal antibodies.

Furthermore 501Y.V2 shows substantial or complete escape from neutralizing antibodies in COVID-19 convalescent plasma. These data highlight the prospect of reinfection with antigenically distinct variants and may foreshadow reduced efficacy of current spike-based vaccines.

          (SNIP)

Discussion 

SARS-CoV-2, the virus responsible for the COVID-19 pandemic is evolving, with new lineages being reported all over the world. Amongst previous lineages, D614G was shown to have faster growth in vitro, enhanced transmission in small animals, and has subsequently become globally dominant28-30. N501Y has been shown to increase affinity for the human ACE2 receptor, which together with the repeated and independent evolution of 501Y containing lineages25,26,31, strongly argues for enhanced transmissibility of these new variants.

Here we show that the 501Y.V2 lineage, that contains nine spike mutations, and rapidly emerged in South Africa during the second half of 2020, is largely resistant to neutralizing antibodies elicited by infection with previously circulating lineages. This suggests that, despite the many people who have already been infected with SARS-CoV-2 globally and are presumed to have accumulated some level of immunity, new variants such as 501Y.V2 pose a significant re-infection risk. 

          (SNIP)

These data also have implications for the effectiveness of SARS-CoV-2 vaccines, which are principally based on immune responses to the spike protein. Neutralizing antibodies have repeatedly been demonstrated as the primary correlate of protection for most vaccines, including those designed to prevent infection with respiratory pathogens34 .

Despite neutralization escape, we show here that a significant proportion of non-neutralizing, RBD binding antibodies remain active against 501Y.V2. While antibody effector functions elicited by infection and vaccination have been implicated in protecting from reinfection and disease35,36, the role of non-neutralizing antibodies and the efficacy of T cell responses to 501Y.V2 remain to be elucidated.

Ultimately, the correlates of protection against SARS-CoV-2 infection and severe COVID-19 disease remain undetermined and rely upon ongoing large-scale clinical trials.

Nevertheless, the speed and scope of 501Y.V2 mediated immune escape from pre-existing neutralizing antibodies highlight the urgent requirement for rapidly adaptable vaccine design platforms, and the need to identify less mutable viral targets for incorporation into future immunogens. 

(Continue . . . )

A sampling of some of the expert reaction posted on the Science Media Centre website (LINK) includes:

Prof Liam Smeeth, Professor of Clinical Epidemiology, London School of Hygiene and Tropical Medicine, said:

“These data are potentially concerning, but it is important to emphasise that these are laboratory findings, and it would be unwise to extrapolate to clinical effects in humans at this stage. The data do raise the possibility that the protection gained from past infection with Covid-19 may be lower for re-infection with the South African variant. The data also suggest that the existing vaccines could be less effective against the South African variant. However, before coming to those conclusions, we need large-scale studies over time among populations where the variant is common looking at re-infection risk and to assess vaccine effectiveness.” 

 

Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, said:

“A variant of the SARS-CoV-2 virus might partially evade immune protection or prior infection. This preprint suggests that individuals might be able to get infected with a variant of SARS-CoV-2 even if they have previously had COVID-19. It also shows we urgently need to find out if we could see infection with this variant post vaccination.

“This study from the National Institute for Communicable Diseases in South Africa shows that the South African virus variant (501Y.V2) is able to escape neutralisation by both monoclonal antibodies (including those being used therapeutically) and by convalescent plasma/sera from previously infected individuals. It is a very thorough study that examines the impact of specific mutations in the spike gene of 501Y.V2 and how these affect the binding of neutralising antibodies. High levels of resistance to convalescent plasma/sera where observed with nearly half (21 of 44, 48%) of the samples having no detectable neutralising activity.

Similarities between the mutations in 501Y.V2 spike and the variant recently found in Brazil suggest that this Brazilian variant will also exhibit significant levels of neutralisation resistance. This study suggests that previously infected individuals may be susceptible to reinfection with virus variants – something which has already been reported in two cases in Brazil. It also has important implications for the effectiveness of current SARS-CoV-2 vaccines which are all based on the original spike gene.

“It is important that we now determine the neutralising ability of antibodies against virus variants generated in response to vaccination and study the immune response in individuals infected with virus variants.”