Vaccine developers move to stay ahead of Covid-19 variants

Yesterday’s US adcom documents provided the first evidence from a large study that an existing Covid-19 vaccine could provide strong protection against the virus’s troublesome South Africa variant. But biopharma is not letting the grass grow under its feet.

Pfizer and Biontech today moved to study a three-dose Comirnaty regimen to tackle variants, as well as mooting a separate variant-specific vaccine, a day after being beaten to the punch by Moderna, which has just shipped the first lots of its next-generation mRNA-1273.351 for clinical trials. At least four other groups are working on similar efforts.

Moderna describes mRNA-1273.351 as a variant-specific booster project designed specifically against the South Africa Covid-19 variant. The first doses have been shipped to the NIH’s NIAID, which is to lead a phase I trial, Moderna said yesterday.

Several approaches are planned: just giving mRNA-1273.351, giving it in several combinations with the existing mRNA-1273 vaccine, or giving three doses of mRNA-1273.

In this regard Pfizer/Biontech’s approach is similar. A current US phase I trial will offer participants an additional, third dose of Comirnaty to investigate its effect on unspecified circulating and “potential newly emerging” Covid-19 variants. Meanwhile, a separate effort will look at developing a next-generation Comirnaty with a modified sequence against the South Africa variant.

Ahead of the curve

Still, why is there a need for new vaccines if current vaccines are working well? Indeed, before J&J’s data yesterday, Moderna and the Pfizer/Biontech group had reported that mRNA-1273 and Comirnaty prompted neutralising antibody production against new variants, in phase I and in vitro respectively.

But it is vital to stay ahead of the curve. Moderna yesterday said it was developing mRNA-1273.351 “out of an abundance of caution”, while Pfizer/Biontech said they had to be prepared for any future strain changes; next-generation Comirnaty is viewed as a blueprint for the companies’ plan to update the current vaccine quickly to address new variants if this need arises.

Earlier this month Glaxosmithkline and Curevac, which have both fallen behind in the Covid-19 vaccine race, teamed up to develop variant-specific, next-generation mRNA vaccines. In January Gritstone said it was working on a second-generation vaccine, and Immunitybio started a South Africa trial of its hAd5 T-cell vaccine, though this does not appear to have been designed specifically against variants.

The South Africa variant, known as 20H/501Y.V2 or B.1.351, is thought first to have emerged last October, and now accounts for the vast majority of Covid-19 cases in that country, as well as being detected in others. It is especially worrying because it causes higher viral load and is more transmissible than early strains.

Already there have been some warning signs over existing vaccines. A South Africa study of Novavax’s NVX-CoV2373 found efficacy of only 50%, versus almost 90% in its UK trial. A separate South Africa trial of Astrazeneca’s AZD1222 found only 10% protection against mild Covid-19, though Astra hopes that the vaccine might still offer protection against severe disease caused by the variant.

A proactive approach by biopharma is warranted.