Two doses of the AstraZeneca Covid-19 vaccine were found to have only a 10.4% efficacy against mild-to-moderate infections caused by the B.1.351 South Africa variant, according to a phase 1b-2 clinical trial published on Tuesday in the New England Journal of Medicine. This is a cause for grave concern as the South African variants share similar mutations to the other variants leaving those vaccinated with the AstraZeneca vaccine potentially exposed to multiple variants. This new finding should force a rapid acceleration of second-generation vaccines and encourage further research into the possibility of a pancoronavirus vaccine.
The trial evaluated the safety and the efficacy of the AstraZeneca vaccine in HIV-negative adults aged between 18 to 64 years old with a median age of 30 years old. The trial was conducted between June 24 and November 9, 2020 in South Africa using a multisite, double-blind, randomized, placebo-controlled approach. Out of the trial’s 750 vaccine recipients, 19 (2.5%) developed mild to moderate COVID-19 more than 14 days after the second dose, compared with 23 of 717 placebo recipients (3.2%). Of the 42 total cases of Covid-19, 39 (93%) were caused by the B.1.351 South Africa variant. These results demonstrated that the AstraZeneca vaccine was only 10.4% effective against the B.1.351 South Africa variant.
It is important to note that there were still no cases of hospitalization for severe Covid-19 or deaths observed in the study. Yet the authors did caution that the relatively young median age of participants (30 years) likely influenced the lack of severe Covid-19 cases.
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The South African B.1.351 shares similar mutations with several other variants. Mutations to positions 417 (K417N), 484 (E484K), and 501 (N501Y) are all located in the receptor-binding domain. This structure is the part of the spike protein that attaches to the ACE2 receptor of the human cell. The K417N and E484K mutations have been seen in the Brazilian and Japanese variants, and N501Y has additionally been seen in the UK variant.
External to the spike protein, there are a set of three deletions in non-structural protein six which also appear in the Brazilian, Japanese, UK, Nigerian, and New York variants. NSP6 is a structural transmembrane protein and these deletions additionally may assist in neutralization escape. NSP2 also carries a common mutation: T85I. This mutation appears in the California variant, the New York variant, and a number of other US variants. While NSP2 has no known function, the pervasiveness of the mutation is notable at the very least. In NSP12, mutation P323L is pervasive in nearly every variant. This protein is the polymerase, which controls viral replication. While it may not aid immune-escape, this mutation certainly aids increased transmissibility of the South African variant and others.MORE FOR YOUNovavax Covid-19 Vaccine Performs Well In Clinical Trials, But Variants Remain A ThreatAntibodies For Covid-19 Found In Breast Milk After VaccineWill Covid-19 Vaccination Disqualify You From Life Insurance? Here Are The Claims
Suffice to say, despite these variants carrying unique sets of mutations, individual changes are shared across lineages that may aid to the neutralization escape the South African variant demonstrates.
As these variants threaten to become the dominant source of coronavirus cases globally, we urgently need second generation vaccines that provide greater protection against the variants if we are going to prevent another wave of infections and return to a level of normalcy. The UK B.1.351 variant and NYC variant B.1.5.26 are now responsible for over 51% of New York Covid-19 cases.
Updates to the AstraZeneca and other Covid-19 vaccines that target the B.1351 variant and others are currently underway. President Biden needs to invoke the power of Operation Warp Speed to rapidly accelerate the development of these vaccines and the logistics involved for rollout within the year. Other countries who are relying on the AstraZeneca vaccine to vaccine the bulk of their population need to do the same, as we have painfully learned no one will be completely protected from Covid-19 until we all are. While we await these updated vaccines, those who have the opportunity should still accept the current AstraZeneca vaccine in order to protect themselves against the risk of hospitalization and death.
In a prior column for Forbes, I wrote about promising research into a pancoronavirus vaccine that protects all variants. This is the long-term goal we should be working towards, if such a vaccine were to come to fruition would no longer need to revise the Covid-19 vaccines each year.