A preprint, an unpublished non-peer reviewed study, from Moderna suggests that their COVID-19 vaccine retains neutralizing activity against emerging variants first identified in the U.K. and in South Africa, and Moderna have announced the launch of a clinical program to boost immunity to emerging variants.
Prof Jonathan Ball, Professor of Molecular Virology at the University of Nottingham, said:
“The finding that sera raised following Moderna vaccination was significantly reduced against the South African variant suggests that this variant might have arisen following immune selection in individuals previously infected with SARS-CoV-2 coronavirus. This highlights the real potential for antibody escape variants to arise in the face of sub-optimal immunity.
“Whilst the vaccine immune sera showed reduced activity it was still able to kill the South African variant virus. We also think that the vaccine is able to generate killer T cells and we hope that these too will still be effective against the variant virus.
“But this data does show that virus evolution can impact on antibody killing, so it will be important to continue to monitor variant emergence and test whether or not genetic changes might impact on key behaviours like antibody sensitivity, transmission and disease severity.
“Importantly the variant that has spread widely throughout the UK was fully susceptible to the Moderna vaccine-induced antibodies. It will also be important to see how immunity raised by the AZ and Pfizer vaccines might be impacted by virus mutation.”
Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:
“These findings are not surprising. The key mutation in the English variant (B.1.1.7) is N501Y is not thought to be an escape mutation and so it is unlikely that it would have any effect on vaccine efficacy. The South African variant (B.1.351) has the N501Y mutation as well but also the E484K mutation which is thought to be an escape mutation and so one would expect some reduced efficacy and this is what has been seen today. Given that the Brazilian variants both contain the E484K mutation it is likely that efficacy to these variants will also be reduced.
“However, this does not mean that existing vaccines will not still be highly effective. Long established human coronaviruses also seem to accumulate mutations over time that ultimately lead to these viruses escaping from the immune protection generated by their ancestors. But each single mutation is unlikely to be sufficient in itself. So we are likely to see gradual accumulation of variants that are more and more able to escape vaccine induced immunity and indeed naturally induced immunity. But this is to be expected and should not pose unsurmountable difficulties for control of the epidemic. Personally I worry more about further mutations that may increase the infectiousness of the virus as this would lead to increased transmission and illness in non-vaccinated individuals.”
Prof Ben Neuman, Chair of Biological Sciences at Texas A&M University-Texarkana, and Visiting Associate Professor at the University of Reading, said:
“This study from Moderna follows two preprints last week that looked at how the new mutations affected vaccine-derived antibodies. Two of the three studies showed that some mutations lessened neutralization but did not knock it out completely.
“It is important to remember that neutralizing antibodies are just one component of an effective immune response, and that while pre-made antibodies like those tested cannot change, a working immune system has some ways to adjust new antibodies in the face of a changing virus. Looking at neutralizing antibodies is convenient and useful, but does not give a full picture of the ways that a person could be protected by vaccination. For example, B cells, T cells and non-neutralizing antibodies can help other parts of the immune system hoover up loose virus particles while rooting out the infected cells where they originate.
“At least for now, it looks like the approved vaccines are quite capable of delivering a reasonable immunity against the full range of circulating SARS-CoV-2 variants. Going forward, it will be important to repeat these tests as new SARS-CoV-2 variants arise, but for now the outlook is hopeful.”
Dr Julian Tang, Honorary Associate Professor/Clinical Virologist, University of Leicester, said:
“This is not an unexpected result – the UK VOC B.1.1.7 variant (with only the N501Y mutation in the S protein RBD – receptor binding domain) has little impact on the Moderna mRNA vaccine efficacy – as was shown in the results of this recent study with the Pfizer mRNA vaccine: https://www.biorxiv.org/content/10.1101/2021.01.18.426984v1
“However, the additional S protein RBD mutations in the South African B.1.351 variant (K417N and E484K – along with the N501Y) do significantly impact the titres (6-fold reduction vs. ‘wildtype’ virus) of the Moderna vaccine required to neutralise the virus in culture.
“But they then go on to state that this is still sufficient to neutralise the virus – though the impact of this depends on how the in vitro pseudovirus data compares with the viral load when a vaccinated person is exposed to the virus in everyday life. This can vary a lot – especially when exposed via aerosol – when in fact, the priming of mucosal IgA antibodies in the respiratory tract probably matter more, where an inhaled vaccine (similar to the primary school child live flu vaccine) may be more effective in generating a protective mucosal immune response. This limitation applies to all the current COVID-19 vaccines which have not really focused on optimising the mucosal IgA response in the respiratory tract – though this type of vaccine design may come later.
“They are also designing a B.1.351-specific vaccine – which just demonstrates how versatile and adaptable this mRNA approach really is.
“Will be interesting to see similar results for the Brazilian B.1.1.28 P1/P2 variants also – which carry the K417T/E484K/N501Y mutations – with both the Pfizer and Moderna mRNA vaccines.”
Dr Simon Clarke, Associate Professor in Cellular Microbiology at the University of Reading, said:
“In this important study, scientist have put the coronavirus spike protein onto other viruses and assessed the ability of vaccine-induced antibodies to stop them invading cells in a manner similar the coronavirus. The ‘UK’ variant (B.1.1.7) was unchanged in its susceptibility to the antibodies, but there was a substantial decrease in the ability of the antibodies to block the entrance of the ‘South African’ variant (B.1.351). The authors of the report do not think this would be enough to stop the vaccines working, but there is no direct assessment on vaccine effectiveness.
“This is a welcome and positive piece of research, but on its own it is not proof that the vaccine will be unaffected by the mutations seen in the ‘South African’ variant. It remains the case that any of the mutations seen in the variant may affect the ability of antibodies to tag the virus for destruction by white blood cells or T cell immunity. Testing the overall effectiveness in real people will provide the definitive answer to whether or not new variants are susceptible to the actions of the vaccines. Further studies with other mRNA vaccines will be needed to see whether or not they are similarly effective against any new variants.”
Prof Jim Naismith, Director of the Rosalind Franklin Institute, and Professor of Structural Biology, University of Oxford, said:
“Consistent with work reported last week, Moderna’s data show the so called South African variant is less susceptible to the antibodies generated by either previous infection or by vaccination. This paper measures a six fold reduction in the response of plasma from vaccinated people, the response is still thought to be strong enough to give some protection. The UK variant is neutralised just as efficiently as the original strain. There is every reason to continue and accelerate the vaccination program. There is no reason to panic.
“Moderna have announced the start of work to deliver a new vaccine against the South African strain. The revolution in vaccine technology that allows such rapid progress against new variants should be celebrated.
“Of course, for those who have died the vaccine has come too late. I am deeply sorry for their families. We need to do our part to drive down the number of infections.”
Prof Lawrence Young, Virologist and Professor of Molecular Oncology, Warwick Medical School, said:
“A new study confirms that the antibody response induced by Moderna’s mRNA vaccine is able to fully neutralise the UK variant of the SARS-CoV-2 virus but is less effective against the South African variant. This preprint presents a thorough laboratory analysis of the ability of antibodies from vaccinated individuals or from non-human primates to block cell infection with pseudotyped viruses (artificial, engineered viruses) carrying different mutations in the SARS-CoV-2 spike protein. It confirms that there is no significant impact on virus neutralisation with the B.1.1.7 variant which is extremely good news given that this is the variant currently fuelling infections in the UK. However the study also shows that, consistent with other recent reports using convalescent plasma, the South African variant is less susceptible to neutralisation with a 6.4 fold reduction in neutralising titre. This effect is likely to impact vaccine efficacy and may also compromise the duration of the protective immune response induced by this vaccine. It is important that we study the neutralising antibody response in individuals infected with the South African and other virus variants. It is likely that these new variants will elicit a protective immune response but that the profile of the antibody response will be different.”
Press Release: https://investors.modernatx.com/news-releases/news-release-details/moderna-covid-19-vaccine-retains-neutralizing-activity-against
All our previous output on this subject can be seen at this weblink:
Prof Jonathan Ball: “Receiving funding to develop a DNA-based Covid19 vaccine, in association with Scancell Ltd.”
None others received.