Scientists study susceptibility of SARS-CoV-2 variants to neutralize antibodies

SARS-CoV-2 variants B.1.1.7 and B.1.351 were first detected in the UK and South Africa respectively, and have since spread to many other countries.

Scientists from the Institut Pasteur have joined forces with the University Hospital of Orléans, the University Hospital of Tours, the University Hospital of Créteil, the Strasbourg University Hospital and the Georges Pompidou University Hospital to study the sensitivity of these two variants to the neutralizing antibodies present in the samples. serum from people vaccinated or previously infected with SARS-CoV-2.

They compared this sensitivity to that of the reference virus (D614G), which was until recently the most common strain in France. Scientists have shown that the British variant is neutralized to the same degree as D614G, while the South African variant is less sensitive to neutralizing antibodies.

To neutralize the South African variant, the antibody concentrations must 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 British variant but less against the South African variant. The study was published in Nature medicine March 26, 2021.

On December 14, 2020, UK authorities informed WHO that a variant (B.1.1.7) had been detected in the south-east of England. In a few weeks, this variant took over from the viral strains circulating in this region and in London. On December 18, 2020, South African authorities reported that a variant (B.1.351) had been detected and was spreading rapidly in three provinces in South Africa.

According to the WHO epidemiological bulletin of February 14, the British and South African variants are now present in 94 and 48 countries respectively. These two variants are considered “variants of interest” and are subject to epidemiological surveillance at the national and international levels.

In a new study, scientists from the Institut Pasteur have joined forces with the Orléans regional hospital, the Tours CHU, the Créteil intercommunal hospital, the Strasbourg CHU and the Georges Pompidou European hospital to study the sensitivity of British and South African variants to antibodies in comparison with the reference strain circulating in France (D614G).

The aim of this study was to characterize the ability of antibodies developed by people vaccinated or previously infected with SARS-CoV-2 to neutralize these new variants.

Scientists isolated the B.1.1.7 and B.1.351 variants of SARS-CoV-2 using samples provided by the National Reference Center for Respiratory Infections Viruses, housed at the Pasteur Institute. Serum samples from 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 effectiveness of neutralization was mainly evaluated using tests with pseudoviruses. We believe that it is crucial to use authentic infectious viral strains in addition to pseudoviruses to assess viral susceptibility to neutralizing antibodies.

In this study, we isolated and used authentic B.1.1.7 and B.1.351 strains and developed a new rapid semi-automated neutralization test based on “reporter” cells which become fluorescent after a few hours of infection “, explains Olivier Schwartz, co-last author of the study and head of the Viruses and Immunity unit at the Institut Pasteur.

The results of the study showed that the British variant (B.1.1.7) was neutralized by 95% (79 of 83) of the serum of people who had been infected with SARS-CoV-2 and whose samples had been taken up to nine months after symptom onset.

The same proportions were observed for the D614G strain, which has been the most common strain in France since the start of the epidemic. In addition, there was no major difference in the antibody concentrations required to neutralize strains D614G or B.1.1.7.

However, scientists noticed a drop in neutralizing activity against the South African variant in 40% of serum samples from individuals who had been exposed to the virus, for samples taken nine months after the primary infection.

They also demonstrated that to neutralize the South African variant (B.1.351), antibody concentrations had to be about six times higher than for D614G.

We have shown that the more rapidly spreading variants, in particular the South African variant, became partially resistant to the antibodies produced after natural infection. This reduced efficacy is particularly visible in individuals with low levels of antibodies. “

Olivier Schwartz, SThis way Co-last author and head of the Virus and Immunity Unit, Institut Pasteur

Research teams also investigated serum samples from people who had been vaccinated with one of the first vaccines used in France (Pfizer-BioNTech COMIRNATY ™). Vaccinated individuals were studied two to four weeks after their first vaccine injection.

The results showed that after two weeks the serum only neutralized strain D614G, while strain B.1.1.7 began to be neutralized at week 3, although less effectively 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 (i.e. one week after the second injection), serum samples from vaccinated individuals were almost as effective against the British variant as against D614G, but remained less effective against the South African variant. 80% of the serum samples were neutralizing for D614G and B.1.1.7, and 60% of the samples were neutralizing for the B.1.351 variant.

“The vaccine generated a neutralizing response that effectively targeted strains D614G and B.1.1.7, despite a delay in the emergence of neutralizing antibodies against B.1.1.7. The efficacy of neutralizing antibodies for strain B. 1,351 was lower, “explained the co-last authors of the study, Sylvie van der Werf, head of the National Reference Center for Respiratory Infection Viruses at the Institut Pasteur, and Thierry Prazuck, Head of the Infectious Diseases Department. of the Orléans regional hospital.

Scientists also analyzed the presence of neutralizing antibodies in nasal samples from vaccinated individuals. They did not observe any neutralizing activity in the nasal mucosa of these people, with the exception of individuals who had already been infected with SARS-CoV-2 before being vaccinated. This suggests that the vaccination does not induce neutralizing antibodies in the nasal mucosa, at least at an early stage after vaccination (four weeks after the first injection).