Project Next Gen: The United States Gets Serious for New Covid Vaccines

New funding and priority: Nasal vaccines, pan-coronavirus vaccines, monoclonal antibodies

Today is a big day.

$5 Billion dollars are allocated to next generation Covid vaccines and therapies.

Those of you who’ve been following my editorials, such as with Akiko Iwasaki calling for Operation Nasal Vaccine, or with Dennis Burton for variant-proof vaccines, or many posts (here, here) and op-eds (here, here) will know I, and many others, have been pleading the case to gear up for better Covid vaccines and therapies. At times my frustration peaked, like with this twitter post last November.

That has now changed. It’s not the ~$18 billion as spent for Operation Warp Speed (OWS), but this is a substantial allocation that should make a difference for accelerating development of nasal and pan-coronavirus vaccines that can be more protective, and durable (both with respect to time and against new variants), along with therapies such as monoclonal antibodies and oral anti-viral pills beyond Paxlovid. Public-industry partnerships (OWS) that have accounted for our early and extraordinary success vs Covid, but until now not replicated. We really need this support.

Why?

1. Shots don’t achieve mucosal immunity. If we’re going to block infections better, we need to induce local immunity through the upper airway by either nasal or oral administration. The rationale to use a nasal spray vaccine as a booster after shots (“prime and spike”) has been well laid out by Iwasaki’s lab, verified in experimental models, reviewed in our editorial, and with approval and rollout of the first nasal vaccine with a randomized trial (by Bharat Biotech, India with intellectual property derived from Washington University, St. Louis). We have also seen last week a comparative study showing nasal vaccine superiority vs shots for induced immunity in the widely accepted and predictive hamster model (twitter post below). Beyond these studies, there are many late stage (Phase 3) nasal vaccine programs that are nearing completion but we haven’t been ready to get behind these in the United States.

   

   

2. The prospects for another Omicron-like event—a new family of variants that will challenge the immunity we have built up via vaccines, boosters, infections and their combinations. As I’ve previously reviewed, the chance of us seeing another highly troublesome variant is estimated to be 10-20% over the next 2 years, and higher as we go beyond that timeline. There are too many paths for this to happen, as shown below, for us not to worry about it. To anticipate this we need a pan-coronavirus vaccine that exploits our knowledge of not just the Spike protein, but also conserved regions of the virus, and a wealth of academic lab studies that have discovered critical antigenic sites (epitopes) of the virus for highly potent, broad, neutralizing antibodies which can serve as templates for such a variant-proof vaccine.

   

   I’ve summarized just some of these reports below

   

We don’t need to “dream” about such a vaccine anymore. (This excellent review was published in Science, April 2021) . With all the science that’s been done, it ought to be attainable! The NextGen program will help accelerate that by promoting and de-risking the vaccine development programs. There are undesirable side effects, some lack of durability of protection beyond 4-6 months, and vaccine-induced injury for current Covid vaccines that can certainly be improved upon.

3. The Immunocompromised have been left behind. We no longer have effective monoclonal antibodies, which could readily be developed as an outgrowth of some of the studies cited above. The only antiviral pill we have is Paxlovid, and while it is effective, it is possible that resistance could develop over time. We need better treatments for people at high-risk, whose immune responses are not optimum or intact.

4. All scientific advances directed against Covid helps in general. Whether it is to identify a strategy to treat or prevent Long Covid, or to help in a future pandemic against another pathogen as I just reviewed for RSV (that markedly accelerated the success of Covid vaccines).

The new Project NextGen didn’t happen by accident. It took many months for the White House Response Team, with efforts led by Dr. Ashish Jha, to first attempt Congressional authorization of funds, and later to successfully get HHS allocation. It also took President Biden to get behind the need and the prioritization.

I’m thrilled to see this getting done. Of course it would have been better to have been initiated a year or two ago, but a foundation of science for the next generation vaccines and therapies has been building. This program and funding can, if properly executed, be a huge catalyst to get us better protected and prepared for the future.

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N.B. I receive no grants for any NextGen vaccines or therapies (and I’m not applying for any) and have no COI related to this post.