While scientists were working on a vaccine, the coronavirus continued to evolve. Although developed in record time, the vaccines were out of sync with the epidemic when they were they were finally available. The Wuhan strain they target gave way to new variants, first D614G in spring 2020, and then a number of other exotic variants since the fall of that year. Pharmaceutical companies have asserted that their formulas are effective against some of these variants, including the one that has spread most rapidly: the English variant. But the news is not so good for others. The South African variant, in particular, is especially resistant to vaccine-induced antibodies. Other variants have since emerged, and their resistance to vaccine-induced neutralizing antibodies remains to be studied.
A study published in Cell provides some answers. Scientists at Massasuchetts General Hospital conducted several experiments to estimate the resistance of 10 coronavirus variants to the neutralizing antibodies of Pfizer and Modern vaccines after one or two doses. As mentioned earlier, the South African variant is among the toughest, but it is not the only one.
Virus-like particles that mimic the variants
The scientists did not use the coronavirus variants directly but used pseudoviruses carrying the mutated S proteins of ten different variants. Therefore, their results concern only the effect of the mutations they performed on the resistance of the neutralizing antibodies. Although the neutralizing antibodies are directed against the S protein, other mutations at other sites in the variants are known to affect resistance as well. As a reminder, a neutralizing antibody is one that acts early in the viral cycle. It prevents the virus from entering its target cell by masking the protein that allows it to enter.
The pseudoviruses, each mimicking a variant of the coronavirus, were added to the serum of people vaccinated with Pfizer and Moderna vaccine after the first or the second dose. For the variants, the researchers chose one or more representatives of the major SARS-CoV-2 strains currently in circulation: the Wuhan reference strain D614G, B.1.1.7 (the English variant), B1.1.298 (the Danish mink variant), B.1.1.429 (the California variant), three variants of strain B.1.351 (the South African variant), P.2 and P.1 (the Brazilian variant). Each of these variants carries different mutations in their S protein and this alters their ability to resist neutralizing antibodies induced by the vaccine.
Some variants escape the neutralizing power of antibodies
The results of this experiment show that, as mentioned earlier, variants of the B.1.351 strain are the most resistant to neutralizing antibodies. After two doses of the Pfizer vaccine, the neutralizing capacity of antibodies is reduced by about 40-fold in the variants of this strain compared with the Wuhan reference strain. And it was about a 20-fold reduction after two injections of the Moderna vaccine. The P1 and P2 strain variants are also less neutralized: about six times less after the second dose of Pfizer vaccine and three times less after the second dose of Moderna vaccine. The other variants also showed resistance, but it was not statistically significant in this study. In addition, the second vaccine injection is essential to strengthening the neutralizing power of the immune system.
These variants are unique in that they have three mutations in the RBD of protein S, compared to only one in other variants that are much better neutralized by vaccine antibodies. But mutations at other sites on the S protein also contribute to the ability of the variants to escape the antibodies, according to the scientists’ observations. They observed this for the South African variant S protein. They made multiple copies of the protein, removed one mutation in the RBD domain in each copy, and kept the others. Without these mutations, the antibodies are able to neutralize the pseudoviruses more easily, but resistance is still present.
This study is imperfect because it does not use the whole of the coronaviruses, but only their S protein expressed by a viral pseudoparticle. If it appears that neutralizing antibodies are less effective against some of them, the immune response is not limited to their action and the S protein is not the only target of the latter. Cellular immunity, especially T cells, attacks other epitopes of the virus to fight infection. In summary, this study confirms observations made several months ago that certain variants are resistant to neutralizing antibodies, although the clinical consequences are not yet known. It also underscores the importance of injecting doses of vaccine into individuals who were not infected with SARS-CoV-2 to induce sufficient neutralizing antibodies to attack the variants.
Although the current vaccines may have lost some of their effectiveness against the new strains they still offer some protection. Based on the results of this study, the Moderna vaccine seems to be the most effective against all the currently circulating strains.