Seeking broad, durable protection, Pfizer and BioNTech move T-cell enhancing COVID vaccine into clinic

Pfizer and BioNTech have opened a new front in their push to develop a better COVID-19 vaccine. After moving a shot with an enhanced spike protein design into the clinic, the partners have now set out to turn another arm of the immune system against the virus by trialing a T-cell enhancing vaccine prospect.

Real-world use of Pfizer and BioNTech’s approved mRNA vaccine Comirnaty has shown how protection fades over time, both because of the emergence of new variants and reductions in antibody levels. The partners, seeking to remain the dominant force as the COVID-19 vaccine market enters its commercial era, have worked this year to develop prophylactics that protect against the pathogen for longer. 

BNT162b4 is one result of the work. The candidate targets highly conserved non-spike proteins to boost and broaden the T-cell response, provide memory T-cell persistence and enhance the durability of the B-cell response. 

Pfizer and BioNTech are testing the vaccine candidate in a phase 1 clinical trial. The study is enrolling 180 adults who have previously received at least three shots of an approved RNA-based COVID-19 vaccine. The subjects will either receive one of three doses of BNT162b4 plus the omicron BA.4/BA.5-adapted Comirnaty bivalent vaccine or just the approved vaccine.

The study design reflects the belief that BNT162b4 may be complementary to Comirnaty and its direct successors, which target the spike protein. By adding a vaccine against non-spike proteins, Pfizer and BioNTech aim to provide broader, more durable protection. Cellular immunity against non-spike proteins could persist even as SARS-CoV-2 evolves and the initial antibody response to Comirnaty wanes. 

Earlier this year, Mikael Dolsten, M.D., Ph.D., chief scientific officer at Pfizer, told investors the goal is to deliver a “COVID-19 vaccine that can provide durable antibody and T-cell immune protection against severe disease and hospitalization for at least one year.” BNT162b4 is one part of the strategy. The other, complementary part is a set of spike protein vaccines designed to protect against as-yet-unseen variants.