For many, one of the defining moments of the COVID-19 pandemic was when they learned that mRNA vaccines developed by Moderna MRNA, +1.46% and BioNTech BNTX, +1.55% and Pfizer PFE, +0.22% were working. Then came the first wave of infections in mid-2021, and there was a gradual realization, both in scientific circles and in the general public, that vaccines were a far less potent protector against infection than we initially thought—even though they worked very well. To prevent serious illness. One way to address the paradox of infection is to improve mucosal immunity, either through an intranasal vaccine — one that is inhaled through the nose — or other methods. Mucosal immunity aims to provide protection at the site of infection—in this case, the mucous membrane of the nose—with systemic immunity provided by an injected vaccine. Several countries are already using vaccines that target mucosal immunity, including China, which began rolling out an inhaled Covid vaccine developed by CanSino Biologics 688185, -1.43% , and India, which in January introduced India as primary or primary. Biotech nasal drops made available. Booster dose. Nasal vaccines are reported in Iran and Russia. No intranasal vaccine has been authorized or approved in the US, although several are in development, including Blue Lake Biotechnology’s experimental vaccine, which is in Phase 1 clinical trials, and CodeGenix’s candidate, which has generated promising data from Phase 3 clinical trials. Both companies are private. Marketwatch interviewed Dr. Dr. Spoke with Joachim Hombach to talk about intranasal vaccines and what they can bring to the table three years into the pandemic. Market Watch: What are the benefits of the nasal vaccine for COVID? Hombach: Intranasal administration may be more convenient than injection and parenteral [non-oral] Administration is number one. Number two is that we expect from a nasal vaccine—because the antigen is given in the mucosa—that we induce mucosal immunity, and our expectation from mucosal immunity is that it does a better job in terms of preventing infection, which in turn will decrease. Transmission intensity. Market Watch: What are the challenges in developing a nasal vaccine? Hombach: We have some mucosal vaccines, including those that are actually already given, such as oral polio. [vaccine]. But they are not directly targeted at the respiratory tract. The best known intranasal vaccine is the influenza vaccine — [AstraZeneca’s
AZN,
+0.02%
] Flumist – which has relatively limited indications but shows that it works better in children than the classical vaccine, but not in adults or adults. The challenge in developing a nasal vaccine is essentially how to evaluate it. You are assessing the impact on transmission. You can evaluate infection reduction, yes, but you’ll also want to actually measure the impact on transmission, and this takes a more complex study. Another problem we have is on the immune side. Specifically, in the context of Covid, we have a reasonable understanding of the relationship between protection against more severe disease and the level of neutralizing antibodies in the bloodstream. This is how vaccines are now being licensed. They are licensed based on immunity criteria. We do not have these immune parameters for mucosal immunity. We can’t really measure it. A significant challenge is how Covid vaccines are brought to market today. Market Watch: So what we’re really talking about are endpoints for clinical trials and criteria for authorization, approval or licensing. Hombach: exactly In some countries, intranasal vaccines are licensed. They are licensed on the basis of neutralizing antibodies in the bloodstream. So they are based on criteria used for classically administered vaccines, which also means that their performance is relative to common clinical endpoints that we evaluate with other vaccines but not to the ones we are interested in. in Market Watch: Is it the responsibility of regulators in different countries or within your organization to set new benchmarks for intranasal-vaccine development? Hombach: I can’t really speak for the regulators, but my understanding is that this is not the case. We’ll go with the criteria we have, but the value-add needs to be studied later in some kind of effectiveness study. We want to get this for any vaccine. But we also want to take it for nasal vaccines. And the data for the license will not provide this information. Market Watch: The US In , we’ve seen several stories about a second operation requiring warp speed [the federal program that spurred the development of the currently available COVID vaccines] Bring better vaccines to market. Is there an appetite to fund or support the development of a new generation of shots given the localized phase of the pandemic we are in now? Hombach: Whether hungry, I don’t know. But if there is a medical or public health need, the answer is clearly yes. We would love it if more investment was made in these vaccines. We have vaccines that work very well for severe disease, but they also have limitations. They have limitations in terms of infection prevention, but also in terms of the durability of the immune response and the breadth of the immune response. Whether an intranasal vaccine would provide benefit here is an entirely different debate. We need innovation in relation to Covid vaccines, and mucosal immunity is one of the key innovations. There is broad-spectrum protection, which probably goes hand-in-hand with more durable protection, because new types are often depleted. Another thing is mucosal immunity so that we can dampen transmission as well. Market Watch: What do you think people still need to understand about vaccines? Are there still challenging messages to get across? Hombach: The concern for us is that we have more and more limitations of a technology, which is mRNA technology, that is working very well. But it is only one, and it is in the hands of very few manufacturers. There are other techniques that have been used successfully. In the market that we have now, they are kind of being pushed aside. This mainly comes from the notion of updating the structure of vaccines, which go faster with mRNA. This is the main advantage of mRNA. For other platforms it takes more time. We have a potentially dangerous narrowing of a technology, and this is probably not good for innovation. Market Watch: What should people think about vaccines in the next year of our lives? Hombach: As we move toward an epidemic, the big question is: What will the vaccination rhythm be in the future? What will be the main target groups of vaccination? [i.e, how many boosters will we need, or which high-risk groups of people will need an extra booster]? We need to admit that, for the time being, we are not in a position to give a definitive answer. But again, back to the initial question, if we had large-scale mucosal vaccines, which would allow really low transmission, the potential for permanent or constant influx of new types would probably decrease. This question and answer has been edited for clarity and length.
