The Great COVID Vaccine Bet

The Great COVID Vaccine Bet

Every gambler will tell you before placing a bet, there is a moment of doubt. It is natural. After all, it is human nature to be cautious of the unknown. And when confronted with uncertainty, we calculate what we believe to be the odds.

Inevitably, this is a subjective exercise. We all perceive risk differently. So the odds are unique to each individual. To compound matters further, not only do we look at risk differently, risk itself changes overtime. It does not take long before the entire process of prediction breaks down into chaos.

This is where we find those at the CDC (Centers for Disease Control & Prevention) in charge of COVID vaccine policies, mulling constantly changing odds that were never fully understood to begin with. As a result, we have those who will jump the line to take any number of booster doses. And we have those who steadfastly refuse to even discuss the topic of vaccines.

But even the most vaccine-happy of us are growing a sense of fatigue with the never ending calls for boosters. It is a sentiment keenly observed among policymakers at the CDC.

“We don’t feel comfortable with multiple boosters every 8 weeks,” said Vaccines and Related Biological Products Advisory Committee Chairman Arnold Monto, MD. “We’d love to see an annual vaccination similar to influenza but realize that the evolution of the virus will dictate how we respond in terms of additional vaccine doses,” he continued.

Simply put, policymakers previously called for additional boosters because they did and still do not know how the virus evolves. And instead of risking more severe infections, the CDC would rather risk its own credibility in calling for more boosters.

We are now at the point where those calls ring hollow. And the CDC has no option but to confront the uncomfortable reality in which it finds itself.

The current vaccines are waning in efficiency along with the public’s trust in CDC recommendations. Next generation, annualized COVID vaccines will likely be available in the Fall, in time for another surge in viral cases, but we are not sure whether they will work – even if they are here.

The CDC has to decide what it will do. It has to place a bet. Should it invest clinical resources and promote public messaging in favor of next generation vaccines; or should it continue along the lines of advocating for more and more boosters?

To determine the best course of action, we should calculate the odds – make a bet. There are two factors at hand with the next generation COVID vaccines. First, will they be ready in time? Second, will they work effectively enough to be good for a full year?

Vaccine stalwarts Pfizer and Moderna have already developed their own versions of a next generation vaccine. Pfizer CEO Albert Bourla said it would be ready to start manufacturing doses of its next generation vaccine as soon as it receives guidance from the FDA. Moderna CEO Stephane Bancel announced its next generation vaccine will be ready by the Fall, and already has data to boot.

“We look forward to sharing initial data on mRNA-1273.214 later in the second quarter [of 2022]. We believe that a bivalent booster vaccine if authorized would create a new tool as we continue to respond to emerging variants”, said Bourla.

Internationally, other COVID vaccine manufacturers are also making their move. CureVac and GlaxoSmithKline (GSK) have developed their own version of a next generation COVID vaccine.

It all sounds so promising. Until we confront the hard reality that the vaccines developed might not be as effective as promised. Clearly, we will have next generation, annualized vaccines ready by the Fall. In fact, we will have an abundance of such vaccines.

But these vaccines are all predicated on certain assumptions – certain odds, if you will – about the evolution of COVID. Some of which we know, but others that remain quite unknown.

“There’s still a lot of science that’s not known,” points out Duke Project program officer Jennifer Gordon, an international program aimed at pooling together resources and research efforts to maximize vaccine effectiveness.

According to the Duke Project, scientists study natural immunity to better anticipate how to optimize acquired immunity. The hope is that a better understanding of the natural immune responses to COVID will ultimately yield better vaccine designs.

But there are trade-offs. Although we have limited the mutation patterns to certain spike proteins on the corona virus, we remain unsure of how we should target those spike proteins. Scientists debate whether we should target slower mutating, more predictable proteins that would make for a weaker, but more certain vaccine; or go for the Hail Mary and target the more virulent, mutagenic proteins, at the risk of overall vaccine efficiency.

It is a game of odds in which scientists gamble mutation rates and vaccine formularies. There will always be trade-offs because there will always be uncertainty. And to heighten things further, there are dollars at stake. Manufacturing the next generation of COVID vaccines will not be cheap, and like before, the federal government will foot the bill. Something the White House seems eager to do, despite a shrinking economy and rampant inflation.

Ashish Jha, MD, White House COVID response chief publicly announced his support to fund the next generation vaccines as soon as possible. He warns the current vaccine strategy of recurrent boosters is losing value and will quickly grow obsolete in terms of immunogenicity and public perception. He is clearly correct, but his reasons for being right – as with all things in the pandemic – are a complex mix of science and politics, forming yet another variable for the CDC.

All of which is to say, the CDC has a lot to weigh as it meets in June to decide whether to move forward with the next generation COVID vaccines. It has to balance finance and politics with public perception and vaccine efficiency. It is not an enviable task, but it is the great bet now placed before the CDC.

And with all bets, there will be moments of doubt. But this time, perhaps we should worry less about being wrong, and consider whether we were ever right in the first place.

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