When the autumn booster programme begins next month, many people are likely to receive Moderna’s new bivalent vaccine, designed to protect against the original Covid strain and the more transmissible Omicron variant. As Covid continues to evolve, so will vaccination strategies. Here we look at some of the developments in the pipeline.

Variant-specific boosters

In the past two years we have watched natural selection in action, with successive strains of Covid emerging, each more transmissible and better able to evade previous immunity than the last. To combat this, vaccine manufacturers have updated vaccines to more closely match strains in circulation, with Moderna’s bivalent vaccine the first to be approved that targets two strains simultaneously (the original variant and Omicron). A Pfizer/BioNTech bivalent vaccine is also under review. These updated vaccines are likely to be more effective (we have yet to get conclusive efficacy data), so they will be valuable for ensuring that people at greatest risk of severe illness remain protected against hospitalisation and death. But there are diminishing returns on deploying these vaccines in the wider population because they do not prevent infection and only prevent symptomatic disease for a few months.

Nasal vaccines

The first generation of Covid vaccines all work by boosting circulating antibodies. But they do little to stimulate antibodies in the tissues that line the nose and airways, and this so-called mucosal immunity is the body’s first line of defence against respiratory infection. This is considered a major weakness of current Covid vaccines and could explain why current vaccines protect against illness and death but not against infection. Scientists hope nasal vaccines, similar to those used for seasonal flu, could overcome this shortcoming and help weaken the chain of transmission and reduce the continued impact of Covid. There are at least 12 nasal vaccines in clinical development, with four in phase 3 trials, and many view an effective nasal vaccine as the next major prize for vaccine research.

Vaccine pills

One company, Vaxart, has developed a tablet that showed promising results in a small trial last month. The aspirin-sized pill uses an adenovirus, similar to the delivery system used by the Oxford/AstraZeneca vaccine, to deliver instructions for making the Covid spike protein to cells in the gut. This stimulates the release of antibodies in the nose and mouth. In the trial, nearly half of volunteers showed higher levels of antibodies in nasal and saliva samples than people whose antibodies were the result of a previous Covid infection. The enhanced antibody levels lasted for six months, according to the trial results. A phase 2 trial with 900 participants is under way and expected to report next year.

Pan-coronavirus vaccines

Last month there was a call from the White House to develop vaccines designed to protect against future Covid-19 variants, and even unknown coronaviruses that could emerge in the future. At the more modest end of the spectrum – although still a major advance on current vaccines – scientists are working on vaccines with broad immunity against current and future Covid-19 strains. These would be designed to sidestep the continual game of catchup with newly emerging variants.

The Walter Reed Army Institute of Research in the US has the only pan-coronavirus vaccine candidate of this type in clinical trials. Other teams are exploring the even more ambitious goal of developing a vaccine that would work for the entire coronavirus family, including the viruses that cause Mers, Sars and seasonal colds. However, achieving this is some way off and is perhaps best viewed as pandemic preparedness research rather than something likely to yield a new Covid vaccine that could be widely deployed in the next year.