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September 13, 2021

Should Covid-19 vaccines ditch the needles? The potential pros (and cons) of intranasal vaccines.

Daily Briefing

    Some fully vaccinated individuals who contract the delta variant can transmit the virus to others, enabling the coronavirus to continue to mutate. This has spurred some health care experts to suggest developing a vaccine that targets the nasal mucosa, Daniel Teres and Martin Strosberg write for MedPage Today.

    Teres is a critical care physician and clinical instructor in public health and community medicine at Tufts University School of Medicine, and Strosberg is emeritus professor of political science, health care policy, and bioethics at Union College.

    Your top resources on the Covid-19 vaccines

      Reducing viral load at the primary point of entry

      According to CDC documents, vaccinated people who are infected with the delta variant may carry just as high a viral load as unvaccinated people. Moreover, the agency documents indicate that those infected with the delta variant have viral loads in their airways tenfold higher than seen in those infected with the alpha variant.

      In response, as hospitals become overloaded with patients despite the widespread availability of vaccines in the United States—and as infection rates from the delta variant continue to rise—some health experts are advocating the development and use of intranasal vaccines, Teres and Strosberg write.

      The authors point out that "systemic vaccines," such as the mRNA Covid-19 vaccines, inject antigen into the muscle and "d[o] not appear to stimulate local mucosal immunity effectively." In comparison, according to Teres and Strosberg, intranasal vaccines can reduce the viral load in the nose and throat and may be able to stimulate local mucosal immunity more effectively than systemic vaccines. 

      The authors also cite a Scientific American opinion piece, written by the Scripps Institute's Daniel Oran and Eric Topol, who highlight several additional reasons to pursue intranasal vaccines, such as "needle phobia," which affects between 20% to 30% of adults, and easier administration compared to current vaccines.

      Disadvantages of intranasal vaccines

      Despite the support for intranasal vaccines, some experts are hesitant because such vaccines use "an attenuated, live Covid-19 virus," Teres and Strosberg write, which poses the "theoretical risk that the vaccine itself can cause the infection." However, the authors point out that such a vaccine "wouldn't be the first vaccine of its kind," as an FDA-approved flu-mist spray for influenza currently deploys an attenuated live quadrivalent influenza vaccine.

      More broadly, however, the authors acknowledge that at present, there are "just a few intranasal vaccines … in necessary clinical trials." Consequently, one major limitation of intranasal vaccines is the amount of time required for development, approval, and distribution, Teres and Strosberg write.

      Intranasal vaccine candidates in development

      Currently, the leading "contender" among the few intranasal vaccines in development is Bharat Biotech's vaccine in India, which is undergoing phase II/III trials using a chimpanzee adenovirus to encode the coronavirus spike protein, Teres and Strosberg write. Additionally, the U.S. National Institutes of Health (NIH) has tested a version of the AstraZeneca/Oxford vaccine repurposed as a nasal spray, and Codagenix, from the Stony Brook University lab, just started phase I clinical trials for a single-dose inhaled vaccine, which uses an attenuated live virus.

      Similarly, in China, CanSino published results of its clinical trial using an aerosol version of its Ad5-nCoV, which has already gained approval as an injectable vaccine. Teres and Strosberg note that an intranasal spray derived from an existing intramuscular vaccine would achieve approval much more easily than a completely new intranasal vaccine.

      While acknowledging that the current vaccines can block most serious infections and death, Teres and Strosberg emphasize the importance of stopping the chain of transmission.

      "Our new priority should be to develop, approve, and distribute prophylactic Covid-19 nasal vaccines that produce protective, local tissue IgA," Teres and Strosberg write. They note that, while currently available systemic intramuscular vaccines "successfully blocked serious and critical infections, … we don't have our lives back together, the economy is faltering, our hospitals are on the verge of burnout and collapse, and people are dying." They conclude, "We need to break the chain of transmission now. We need to invest in something different. … [T]he NIH, private sector, and philanthropies must invest in intranasal vaccine research and support expansion of adaptive clinical trials." (Teres/Strosberg, MedPage Today, 9/5)

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