Wednesday, April 21, 2021

Mutation worry grows for vaccines

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A particular mutation of the Sars-Cov-2 virus is established to lower the efficacy for vaccines, the results announced by Novavax on Thursday and Johnson & Johnson (J&J) on Friday showed, reinforcing concerns that the inoculations may need to be updated to fight these new variants.

The results also appear to reinforce the notion that vaccines that elicit higher immunogenicity – measured as antibody titers — could be leading to higher efficacy. These insights are crucial as countries strike deals and prioritise different vaccines, particularly as they race to stay ahead of the coronavirus’s evolution.

The mutation particularly worrying experts is known as E484 and occurs in the spike protein, the component of the virus used to enter target cells. It has been found in two widely spreading variants – the B.1.351 in South Africa and P.1 in Brazil.

Novavax, which said its dose was 96% effective in preventing disease with the older variant, said the efficacy dropped to 60% in a small trial in South Africa where B.1.351 accounted for most infections. In the case of the J&J-Janssen dose too, the efficacy rate was 57% (for the SA strain) compared to 72% in the US, where infections were with the older variant.

“Novavax initiated development of new constructs against the emerging strains in early January and expects to select ideal candidates for a booster and/or combination bivalent vaccine for the new strains in the coming days. The company plans to initiate clinical testing of these new vaccines in the second quarter of this year,” the company said in a statement, confirming that it had started work on updating the dose.

On January 25, Moderna became the first to begin work to account for the new mutation, after reporting that it had seen a drop in immunogenicity in lab tests when the South African variant was used.

“We now know that there is some loss in vaccine efficacy, down to around the 50%-60% level,” said John P Moore, leading virologist and professor at Cornell University’s Weill Cornell Medicine over email.

“But that’s not zero, and a year ago we would have settled for a 50%-60 % effective vaccine,” he added.

“The low efficacy of the Novavax vaccine candidate against the B.1.351 is concerning. However, the data is also reassuring in many ways. First, the vaccine itself worked very well against the ’old’ Sars-CoV-2 variants and the B.1.1.7 (UK) variant… And, vaccine efficacy against B.1.351 seemed markedly reduced, but still present. This was against symptomatic disease in general. It is very likely, that the efficacy against severe disease is much higher,” said Florian Krammer, professor of microbiology at the Icahn School of Medicine at Mount Sinai Hospital in New York, in a series of tweets on Friday.

The results by J&J and Novavax also showed that vaccines that led to significantly higher volumes of antibody when compared to people who recovered appear to be showing higher efficacy rates. For instance, the three vaccines that reported manifolds more antibody titre levels – Pfizer/BioNTech, Moderna and Novavax (see box) – had efficacy rates in the mid 90s.

In comparison, the single-dose J&J-Janssen vaccine and the Oxford-AstraZeneca vaccine – both of which showed antibody levels comparable to a natural infection – had lower efficacy rates. Experts have said that while higher efficacy rates are better, those with lower ones will still be able to protect from severe disease or death.

Speaking in the context of J&J’s lower apparent efficacy, Moore said: “Look, a year ago, we are all hoping for efficacy in the 60-70% range. The mRNA and now Novavax data have spoiled us, as we now ‘expect’ 90-95%… Lesser efficacy will still be useful.”

But, he added, “there are going to be complications — what will the public want/expect/use? Will there be controversies there? And infected vaccine recipients may be a problem area for generating resistant variants.”


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