The B.1.1.7 and B.1.351 variants of SARS-CoV-2 were first detected in the UK and South Africa respectively, and have since spread to many other countries. Scientists from the Institut Pasteur joined forces with Orléans Regional Hospital, Tours University Hospital, Créteil Intercommunal Hospital, Strasbourg University Hospital and Georges Pompidou European Hospital to study the sensitivity of these two variants to neutralising antibodies present in the serum samples of people who have been vaccinated or previously infected with SARS-CoV-2. They compared this sensitivity with that of the reference virus (D614G), which was until recently the most widespread strain in France.
The scientists demonstrated that the UK variant is neutralised to the same degree as D614G, whereas the South African variant is less sensitive to neutralising antibodies.
To neutralise the South African variant, the antibody concentrations need to be six times higher than for D614G. This difference in sensitivity was also observed in vaccinated individuals; the antibodies in their serum are effective against the UK variant but less so against the South African one.
On 14 December, 2020, the UK authorities informed WHO that a variant (B.1.1.7) had been detected in the south east of England. Within a few weeks, this variant took over from the viral strains circulating in this region and in London. On December 18, 2020, the South African authorities reported that a variant (B.1.351) had been detected and was spreading rapidly throughout three provinces of South Africa. According to World Health Organisation's epidemiological bulletin dated 14 February, the UK and South African variants are now present in 94 and 48 countries respectively. These two variants are considered to be 'variants of interest' and are subject to epidemiological surveillance at national and international levels.
The aim of this study was to characterise the capability of antibodies developed by people who had been vaccinated or previously infected with SARS-CoV-2 to neutralise these new variants.
The scientists isolated the SARS-CoV-2 variants B.1.1.7 and B.1.351 using samples provided by the National Reference Centre for Respiratory Infection Viruses, hosted at the Institut Pasteur. Serum samples of people who had been vaccinated or previously exposed to SARS-CoV-2 were used to study the sensitivity of the variants to the antibodies present in this serum.
"Previously, the efficacy of neutralisation had been mainly assessed using tests with pseudo-viruses. We believe that it's crucial to use authentic infectious virus strains in addition to pseudo-viruses to assess viral sensitivity to neutralising antibodies. In this study, we isolated and used authentic B.1.1.7 and B.1.351 strains and developed a novel rapid semi-automated neutralisation assay based on 'reporter' cells that turn fluorescent after a few hours of infection," explained Olivier Schwartz, co-last author of the study and head of the virus and immunity unit at the Institut Pasteur.
The results of the study showed that the UK variant (B.1.1.7) was neutralised by 95% (79 out of 83) of the serum of people who had been infected with SARS-CoV-2 and whose samples were taken up to nine months after the onset of symptoms. The same proportions were observed for the D614G strain, which has been the most widespread strain in France since the start of the epidemic. Moreover, there was no major difference in the antibody concentrations required to neutralise the D614G or B.1.1.7 strains.
However, the scientists noticed a decline in neutralising activity against the South African variant in 40% of the serum samples of individuals who had been exposed to the virus, for samples taken nine months after the primary infection.
They also demonstrated that to neutralise the South African variant (B.1.351), the antibody concentrations needed to be approximately six times higher than for D614G. "We showed that the faster-spreading variants, particularly the South African one, have become partially resistant to the antibodies produced after a natural infection. This reduced efficacy is particularly visible among individuals with low antibody levels," commented Schwartz.
The research teams also investigated the serum samples of people who had been vaccinated with one of the first vaccines used in France (Pfizer-BioNTech COMIRNATY™). The vaccinated individuals were studied two to four weeks after their first vaccine injection. The results showed that after two weeks, the serum only neutralised the D614G strain, whereas the B.1.1.7 strain started to be neutralised at week 3, although less efficiently than D614G. The anti-B.1.351 response was negative up to week 3 and could be detected at week 4.
Four weeks after the first vaccine injection (one week after the second injection), the serum samples of the vaccinated individuals were almost as effective against the UK variant as against D614G, but remained less effective against the South African variant. 80% of the serum samples were neutralising for D614G and B.1.1.7, and 60% of the samples were neutralising for the B.1.351 variant.
"The vaccine generated a neutralising response that efficiently targeted the D614G and B.1.1.7 strains, despite a delay in the emergence of neutralising antibodies against B.1.1.7. The efficacy of neutralising antibodies for the B.1.351 strain was lower," explained the co-last authors of the study, Sylvie van der Werf, head of the National Reference Centre for Respiratory Infection Viruses at the Institut Pasteur, and Thierry Prazuck, head of the infectious diseases department at Orléans Regional Hospital.
The scientists also analysed the presence of neutralising antibodies in the nasal samples of vaccinated individuals. They did not observe any neutralising activity in the nasal mucosa of these people, apart from in individuals who had already been infected with SARS-CoV-2 prior to being vaccinated. This suggests that vaccination does not induce neutralising antibodies in the nasal mucosa, at least at an early stage after vaccination (four weeks after the first injection).
Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies
Delphine Planas, Timothée Bruel, Ludivine Grzelak, Florence Guivel-Benhassine, Isabelle Staropoli, Françoise Porrot, Cyril Planchais, Julian Buchrieser, Maaran Michael Rajah, Elodie Bishop, Mélanie Albert, Flora Donati, Matthieu Prot, Sylvie Behillil, Vincent Enouf, Marianne Maquart, Mounira Smati-Lafarge, Emmanuelle Varon, Frédérique Schortgen, Layla Yahyaoui, Maria Gonzalez, Jérôme De Sèze, Hélène Péré, David Veyer, Aymeric Sève, Etienne Simon-Lorière, Samira Fafi-Kremer, Karl Stefic, Hugo Mouquet, Laurent Hocqueloux, Sylvie van der Werf, Thierry Prazuck, Olivier Schwartz
Published in Nature Medicine on 26 March 2021
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.7 and B.1.351 variants were first identified in the United Kingdom and South Africa, respectively, and have since spread to many countries. These variants harboring diverse mutations in the gene encoding the spike protein raise important concerns about their immune evasion potential. Here, we isolated infectious B.1.1.7 and B.1.351 strains from acutely infected individuals. We examined sensitivity of the two variants to SARS-CoV-2 antibodies present in sera and nasal swabs from individuals infected with previously circulating strains or who were recently vaccinated, in comparison with a D614G reference virus. We utilized a new rapid neutralization assay, based on reporter cells that become positive for GFP after overnight infection. Sera from 58 convalescent individuals collected up to 9 months after symptoms, similarly neutralized B.1.1.7 and D614G. In contrast, after 9 months, convalescent sera had a mean sixfold reduction in neutralizing titers, and 40% of the samples lacked any activity against B.1.351. Sera from 19 individuals vaccinated twice with Pfizer Cominarty, longitudinally tested up to 6 weeks after vaccination, were similarly potent against B.1.1.7 but less efficacious against B.1.351, when compared to D614G. Neutralizing titers increased after the second vaccine dose, but remained 14-fold lower against B.1.351. In contrast, sera from convalescent or vaccinated individuals similarly bound the three spike proteins in a flow cytometry-based serological assay. Neutralizing antibodies were rarely detected in nasal swabs from vaccinees. Thus, faster-spreading SARS-CoV-2 variants acquired a partial resistance to neutralizing antibodies generated by natural infection or vaccination, which was most frequently detected in individuals with low antibody levels. Our results indicate that B1.351, but not B.1.1.7, may increase the risk of infection in immunized individuals.