Researchers at the Francis Crick Institute and University College London Hospitals NHS Foundation Trust (UCLH) have studied whether antibodies produced as a result of infection with one SARS-CoV-2 variant are able to bind to and neutralize other variants.
Over the course of the pandemic, various COVID-19 variants have arisen with the Delta variant currently dominant in the UK. Understanding how some variants may be able to trigger an effective antibody response against other variants, in addition to itself, could help inform future vaccine design.
In their study, published in eLife (29 July), the scientists analyzed blood samples collected from patients who had previously been infected with COVID-19 and who were admitted to UCLH for other reasons, samples from health care workers as well as samples collected from patients at different points earlier in the pandemic.
The study included:
- The original strain first discovered in Wuhan, China
- The dominant strain in Europe during the first wave in April 2020 (D614G)
- B.1.1.7, the variant first discovered in Kent, UK (Alpha)
- B.1.351, the variant first discovered in South Africa (Beta)
While antibodies produced by one variant were able to bind to other variants at a similar rate, there were some differences in whether antibodies could neutralize other variants. If an antibody is able to neutralize a virus, this means it can stop the virus from entering the hosts cells in order to replicate.
The researchers found that antibodies produced by the Alpha variant were not able to neutralize the original or D614G strains as effectively, in comparison to neutralizing the Alpha variant itself.
Antibodies produced against infection with the D614G strain were able to neutralize both the Alpha and original strains to a similar level as D614G.
Both the Alpha and D614G strains produced antibodies which were not able to effectively neutralize the Beta strain.
There are many elements of the immune system which impact how protected an individual may be against future disease. This includes memory B cells and T cells which equip the immune system to deal with evolving threats. As a result, these findings do not necessarily mean people who were infected with specific variants are less protected against others.
Kevin Ng, co-first author and Ph.D. student in the Retroviral Immunology Laboratory at the Crick says: “It’s important to note that most people who have been infected with the virus will not know which variant they were infected with and it is critical that everyone eligible for the vaccine takes up the opportunity because we know they are effective in some way against all known variants.”
As the antibodies were able to bind to other variants at a similar level, but had differing ability to neutralize other strains, this suggests that there are only a few regions on the spike of the virus which are important to this neutralization process. It is the mutations within these key sites which impact the ability of antibodies produced by one variant to neutralize another.
Nikhil Faulkner, co-first author and Ph.D. student in the Retroviral Immunology Laboratory at the Crick says: “As the pandemic continues and more variants may arise, research into how infection with one variant impacts immune responses to other variants is important.
“This could help inform experts who are studying and deciding which variants should be included in future booster vaccines. By creating a multivalent vaccine, like with the annual flu shot, we could factor different variants into a single vaccine. This would help to increase the breadth of immune protection against current and future variants.”
We studied the cross-reactivity of monoclonal antibodies to pre-existing SARS-CoV-2 strains, sera from convalescent individuals six or twelve months after the onset of COVID-19 symptoms and sera from recent recipients of a COVID-19 vaccine against an infectious Delta isolate. Some monoclonal antibodies, including bamlanivimab, lost their ability to bind to the spike protein and no longer neutralized the Delta variant.
We also showed that the Delta variant is less sensitive to sera from naturally immunized individuals. Vaccination of convalescent individuals boosted the humoral immune response to well above the threshold of neutralization. These results strongly suggest that vaccination of previously infected individuals is likely to be protective against a large array of circulating viral strains, including the Delta variant.
In individuals who had not previously been infected with SARS-CoV-2, a single dose of either the Pfizer or the AstraZeneca vaccine induced a barely detectable level of neutralizing antibodies against the Delta variant. About 10% of the sera neutralized this variant. However, a two-dose regimen generated high sero-neutralization levels against the Alpha, Beta and Delta variants in individuals sampled at week 8 to week 16 after vaccination.
Levels of neutralizing antibodies are highly predictive of immune protection from symptomatic SARS-CoV-2 infection25. A recent report analysing all sequenced symptomatic cases of COVID-19 in England was used to estimate the effect of vaccination on infection26. Effectiveness was notably lower for the Delta variant than for the Alpha variant after one dose of the AstraZeneca or the Pfizer vaccine.
The two-dose effectiveness against the Delta variant was estimated to be 60% and 88% for the AstraZeneca and the Pfizer vaccine, respectively26. Our neutralization experiments indicate that antibodies elicited by the Pfizer and AstraZeneca vaccines are efficacious against the Delta variant, but about three- to fivefold less potent than they are against the Alpha variant. There was no major difference in the levels of antibodies elicited by the Pfizer or the AstraZeneca vaccines.
Potential limitations of our work include the low number of vaccinated individuals analysed and the lack of characterization of cellular immunity, which may be more cross-reactive than the humoral response. Future work with more individuals and longer survey periods will help to characterize the role of humoral responses in the efficacy of vaccines against circulating variants.
Our results demonstrate that the emerging Delta variant partially—but notably—escapes neutralizing monoclonal antibodies and polyclonal antibodies elicited by previous infection with SARS-CoV-2 or by vaccination.
reference link: https://www.nature.com/articles/s41586-021-03777-9
More information: Nikhil Faulkner et al, Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains, eLife (2021). DOI: 10.7554/eLife.69317