Variant specific boosters
Over the past two years we have watched natural selection in action, with successive strains of Covid emerging, each more contagious and better able to evade previous immunity than the last. To combat this, vaccine makers have updated vaccines to better match the strains in circulation, with Moderna’s bivalent vaccine being the first to be approved that targets two strains at once (the original variant and Omicron). A Pfizer/BioNTech bivalent vaccine is also under consideration. These updated vaccines are likely to be more effective (we don’t yet have conclusive efficacy data), so they will be valuable in ensuring that people at greatest risk of serious illness remain protected from hospitalization and death. However, there are diminishing returns from developing 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 work by boosting circulating antibodies. But they do little to stimulate antibodies in the tissues lining the nose and airways, and this so-called mucosal immunity is the body’s first line of defense against respiratory infection. This is considered a major weakness of current Covid vaccines and could explain why current vaccines protect against disease and death but not infection. Scientists hope that nasal vaccines, similar to those used for seasonal flu, could overcome this drawback and help weaken the chain of transmission and reduce the ongoing impact of Covid. There are at least 12 nasal vaccines in clinical development, with four in phase 3 trials, and many see an effective nasal vaccine as the next big prize for vaccine research.
Vaccine pills
One company, Vaxart, 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 instruct intestinal cells to produce the Covid spike protein. This stimulates the release of antibodies in the nose and mouth. In the trial, almost half of the volunteers showed higher levels of antibodies in nasal and saliva samples than people whose antibodies were the result of a previous Covid infection. The elevated antibody levels lasted for six months, according to the test results. A phase 2 trial with 900 participants is ongoing and expected to be published next year.
Panic coronavirus vaccines
Last month there was a call from the White House for the development of vaccines designed to protect against future variants of Covid-19, and even unknown coronaviruses that could emerge in the future. At the more modest end of the spectrum—though still a significant advance on current vaccines—scientists are working on vaccines with broad immunity against current and future Covid-19 strains. These will be designed to bypass the constant game of catchup with newly emerging variants. The Walter Reed Army Institute of Research in the US has the only pancoronavirus vaccine candidate of this type in clinical trials. Other groups 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 next year.
