Pfizer vaccine is less effective against the South African strain

An Israeli study has indicated the Pfizer-BioNTech COVID-19 vaccine is less effective against the so-called South African variant of the virus.

The study by scientists from Ben-Gurion University of the Negev said that the vaccine produces high levels of antibodies that efficiently combat both the generic strain of the virus and the British variant.

The vaccine only moderately neutralized the South African variant, however. It was also less effective against strains that had attributes of both the British and the South African variants.

The researchers collected blood samples from 10 people who recovered from COVID-19, five people who received the first dose of the vaccine, and 10 people who also received the second. Samples were drawn from participants 21 days after the first dose, or 10 days after the second.

They then measured the antibodies’ ability to protect against infection.

“Our study validates the clinical efficacy of the Pfizer vaccine, but raises concerns regarding its efficacy against specific SARS-CoV-2 circulating variants,” the authors wrote. “Overall, these results call for a close attention of variant spread, and a [possibility] for new vaccines with improved neutralizing potency against SARS-CoV-2 variants.”

SARS-CoV-2 is the name of the coronavirus that causes the disease COVID-19.

“Our findings show the vaccine is less effective against the South African strain, but the efficacy still exists,” said lead researcher Ran Taube.

The study said antibodies of people who have received vaccines appear more resistant to the virus, including its variants, than antibodies of people who recovered from the virus.

The spread of the variants was likely due to their higher levels of infectivity, and not resistance to vaccines, they said.

The researchers found an elevenfold increase in antibody levels for people who had completed vaccine treatment relative to people who had recovered from the virus, and far higher levels than for people who had only received the first vaccine dose, suggesting the full treatment is necessary for a high level of protection.

People who recovered from the virus were also less protected against the South African strain than the British variant.

The authors said people who had been infected by the South African variant were probably unlikely to get reinfected by the same variant.

The study used pseudoviruses, or a laboratory-safe virus particles that do not replicate, presenting a possible limitation to the results. The use of pseudoviruses for evaluating antibodies was previously established and earlier studies of the SARS-CoV-2 virus validated the use of pseudoviruses in research, the authors noted.

The study was published on Saturday in the peer-reviewed scientific journal Cell Host & Microbe. The researchers are from Ben Gurion University’s Shraga Segal Department of Microbiology and Immunology.

Israel’s vaccine campaign, which has vaccinated most eligible adults, relies mostly on the Pfizer vaccine.

The entrance of vaccine-resistant variants has been a top concern for Israeli officials and spurred the government to tightly limit international travel for much of the pandemic, including a months-long shutdown of Ben Gurion Airport, even to most Israeli citizens.

Most infections in Israel are caused by the British strain of the virus.

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One year in the coronavirus disease 2019 (COVID-19) pandemic, the first vaccines are being rolled out under emergency use authorizations. Recently, rapidly spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, have been reported.

It is of great concern that these newly emerging variants can escape neutralizing antibodies induced by previous infection and/or vaccination through mutations in the spike (S) protein, including the receptor binding domain (RBD), a target for neutralizing antibodies.

We and others have previously reported that the asparagine (N) to tyrosine (Y) substitution at position 501 (N501Y), present in variants of concern belonging to the B.1.1.7, B.1.351 and P.1 lineages, does not seem to affect in vitro neutralization of SARS-CoV-2 viruses by human sera from convalescent or vaccinated human donors.

However, there remains concern about additional substitutions like E484K present in B.1.351 and P.1 lineages allowing escape from neutralizing antibodies (1–4), thereby potentially rendering vaccine-induced immunity less protective.

In order to investigate the impact of the E484K mutation in the neutralizing activity of SARS-CoV-2 specific antisera, we performed in vitro microneutralization assays with both the USA-WA1/2020 virus and a recombinant (r)SARS-CoV-2 virus that is identical to USA-WA1/2020 except for the E484K mutation introduced in the spike RBD.

The E484K mutant rSARS-CoV-2 was generated using previously described reverse genetics based on the use of a bacterial artificial chromosome (BAC) (5–7). The USA-WA1/2020 reflects SARS-CoV-2 strains that circulated in the early phase of the COVID-19 pandemic. A total of 34 sera were selected from study participants based on their SARS-CoV-2 S enzyme linked immunosorbent assay (ELISA) antibody titer (negative [N=4] versus weak [N=8], moderate [N=11] or strong positive [N=11]).

In addition, we included sera from five individuals who received two doses of the Pfizer SARS-CoV-2 vaccine BNT162b2 (V1-V5). Demographics and available metadata for each participant is summarized in Supplementary Table 1. We performed all experiments in a blinded manner. The same sera have been tested for neutralization studies with a N501Y SARS-CoV-2 variant in our recent report (8).

Results

Sera from vaccinated donors gave high neutralization titers, similar to convalescent samples with the highest neutralization titers. Serum neutralization efficiency was lower against the E484K rSARS-CoV-2 (vaccination samples: 3.4 fold; convalescent low IgG: 2.4 fold, moderate IgG: 4.2 fold and high IgG: 2.6 fold based on geometric means) which was significantly different for the convalescent sera (see Figure 1), suggesting that the single E484K mutation in the RBD affects binding by serum polyclonal neutralizing antibodies from both convalescent and vaccinated donors.

In the case of convalescent donor sera with low or moderate IgG against SARS-CoV-2 S protein, the drop in neutralization efficiency could result in neutralization ID50 values similar to negative control samples, resulting in low or even absence of neutralization of the E484K recombinant virus by those sera.

Conclusions

These data indicate that the E484K mutation present in circulating SARS-CoV-2 strains that belong to the B.1.351 and P.1 lineages reduces the neutralizing activity of human polyclonal sera induced in convalescent (infected with previous strains) and vaccinated individuals.

The significant impact of a single point mutation in the neutralizing activity of polyclonal sera highlights the need for the rapid characterization of SARS-CoV-2 variants. However, human sera with high neutralization titers against the USA-WA1/2020 strain were still able to neutralize the E484K rSARS-CoV-2.

Therefore, it is important to aim for the highest titers possible induced by vaccination, as this should enhance the chances for protection even in the case of antigenic drift of circulating SARS-CoV-2 strains. Currently deployed SARS-CoV-2 vaccines are recommended as a prime-boost regimen. Because of vaccine shortage and relatively strong seroconversion being observed after a single dose, some public health authorities recommended to postpone the second booster vaccination in order to be able to provide more individuals with a first primer vaccination.

This will result in lower neutralizing antibody titers. Our data show that this may be problematic in the context of newly emerging SARS-CoV-2 variants, as it may leave some vaccinees unprotected. It is currently unknown which neutralization titer correlates with (full) protection, and to what extent immune mechanisms beyond direct virus neutralization contribute to protection, especially for specific target groups with comorbidities that are currently being prioritized for vaccination.

Viruses that belong to the B.1.351 and P.1 lineages have originally been described in the Republic of South Africa and Brazil, but are now reported on multiple continents already. Therefore, while it is premature to update vaccines based on these lineages, it is important that the worldwide vaccination effort will aim at fully vaccinating as many people as possible using vaccination strategies that result in induction of high neutralizing antibody titers.

reference link: https://www.medrxiv.org/content/10.1101/2021.01.26.21250543v1.full