The speed at which highly effective Covid vaccines were developed was almost miraculous. But here we are, two-and-a-half years into the pandemic, and the vaccines we thought might end our global nightmare have not done so. One of the biggest reasons is that current vaccines, while excellent at preventing severe disease, generally do not prevent transmission of the virus.

Scientists who study the inner workings of our immune system have pushed throughout the pandemic for different delivery strategies. Current vaccines are designed for intramuscular delivery — that arm jab many of us have experienced. This approach induces the creation of antibodies that circulate throughout our body, triggering an immune response that protects us when viruses enter cells in our bloodstream, organs, and other tissues.


But many immunologists argue that these vaccines miss an important opportunity to defend us at the place where the virus typically first attacks us: the mouth and nasal passages. Those widely-circulating vaccine-triggered antibodies rarely make it to these areas with mucosal linings, biological zones where defenses are typically marshaled through sticky mucus more than through circulating antibodies. What if we could deploy antibodies as gatekeepers at our most vulnerable entry points, not only to protect against infection but also to prevent transmission? This could address what scientists Eric Topol and Akiko Iwasaki called today’s “leaky” vaccines in a recent Science editorial.

The concept isn’t new to the vaccine world, but it remains largely unproven. There is one FDA-approved nasal vaccine today — FluMist, a flu vaccine that’s sprayed up the nose but is not recommended for groups including the immunocompromised, pregnant, or those older than 50. Even scientific champions of nasal vaccines acknowledge that significant progress must be made in developing and testing this type of vaccine before it can become more common. Most nasal vaccines haven’t even yet reached phase 3 trials, so there isn’t good data about their effectiveness over extended periods (though scientists hope they will remain effective for long periods like injected vaccines do).

But Covid has spurred renewed interest, and scientists around the world have made tremendous efforts to overcome existing challenges. Globally there are now at least a dozen nasal Covid vaccines in clinical trials; four have reached phase 3 trials, which are generally the final step before a vaccine can be submitted for regulatory review with a health agency.


At Yale University, scientists including Iwasaki have proposed an approach they call “prime and spike.” The method would start with the usual intramuscular Covid vaccine to achieve systemic protection, then be followed by a nasal vaccine, to deliver strong protection in the respiratory tract. Their paper, which has not yet been published in a peer-reviewed journal, reports results from a study in mice that elicited a robust immune response throughout the body and specifically in the mucosal respiratory tissues. Other research teams have reported similar findings.

“The world desperately needs a vaccine strategy that places immunological guards outside the gates to prevent viral invaders from infecting us,” Iwasaki wrote in a New York Times opinion piece. “While there are some remaining obstacles, the potential immunological and public health benefits of nasal spray vaccines are worth focusing on now and for years to come.”

But the new group of nasal vaccines has not received the levels of government funding and fast-tracked development that were showered on the first batch of Covid vaccines, and that is limiting the pace of progress. That’s why scientists like Topol and Iwasaki are now calling for a program like Operation Warp Speed to accelerate the development of nasal vaccines for Covid.