Novavax’s Manufacturing Issues Are Solvable, But Covid-19 Vaccine Herd Immunity May Not Be

In the last 24-hours vaccine makers, Moderna and Novavax both released positive, but limited information emphasizing the strengths of their respective vaccines over separate 6-month periods. Additionally, Novavax issued some not so positive news that there were some FDA manufacturing issues the US Government had asked the company to resolve, and I am quite certain that these are solvable hurdles. What was of greater interest was information released by both companies on their individual progress with booster candidates, and therein the real Covid-19 discussion must begin.

As a forward, vaccines are still the most effective FDA authorized defense we now have against the SARS-CoV-2 virus that causes Covid-19 infections, but that defense weakens over time. One measure of vaccine strength is the level of neutralizing antibodies. Recent studies confirm that there is a difference in antibody protection between those who were vaccinated and those who have recovered from a Covid-19 infection. Antibody counts in those who have received a vaccine decline more rapidly than the counts in patients recovering from acute infections.

If that is the case, why not administer booster injections to counter the decline in the vaccinated population? A recent study by The Rockefeller University suggests that boosters may not bolster defenses to the degree needed to protect from infection. The researchers analyzed patients convalescing from acute SARS-CoV-2 infections and found that they produced B-cell responses for up to a year after infection. During that year, so-called memory cells not only increased in absolute numbers, but also produced broad and potent antibodies that were active in fighting both the original virus and to many of the variants. When convalescing patients then received an mRNA vaccine after initial recovery, they produced even higher levels of plasma neutralizing antibodies. However, in naïve (not previously infected) individuals, the administration of a vaccine followed by a booster also increased the quantity of antibodies, but the antibodies lacked the potency of those produced in previously infected patients who received subsequent mRNA vaccination.

As such, the probability of a vaccine strategy providing “Herd Immunity” has moved from arguable to improbable. Part of the problem is that SARS-CoV-2 is not following the patterns of previous influenza epidemics. It is not a flu that peaks and then disappears within weeks or months. This is an ever shape-shifting virus, finding new ways to outmaneuver our defenses as evidenced by the occurrence of so-called breakthrough infections. Simply being vaccinated does not ensure that one will not become infected, spread the virus, or become ill (albeit with milder symptoms). Recent data from Israel, the UK, and Provincetown, MA, show the limits of vaccine protection. We must realize that Covid-19 vaccines are now prophylactic therapeutics that mitigate, and sometimes prevent the most serious consequences of SARS-CoV-2 infection.

Am I saying vaccines are useless? Of course not. Vaccines confer their protection by stimulating T cells and B cells which, in turn, produce the neutralizing antibodies that keep the virus at bay. We must realize that keeping the virus at bay may buy us time, but it does not guarantee long-term success. Restraining the virus through vaccination also allows the new variants to evolve, so the virus can survive, thrive and eventually become dominant, just as the Delta variant has done.

The current Delta variant is much more easily transmitted to vaccinated and unvaccinated alike. Not surprisingly, it is most harmful to the unvaccinated. But there are many more letters in the Greek alphabet. In Peru, investigators are studying the Lambda variant, which is feared to be more transmissible and, worse, better at evading current vaccines. Lambda has already spread to several other countries, including the United States.

CDC internal unreleased data is addressing whether our current vaccine strategy can remain viable in its current form and is being reviewed by the administration. Striking new information in this data suggests that breakthrough infections seem to start as early as five months after vaccination. The full data must be released, and soon, to inform scientists, politicians and the public at large to enable long-term planning. As unpleasant as it may be, Covid-19 will be with us, in some form, for several years to come. We must adjust our attitudes and our strategies to deal with this new reality.

Israel began its mass vaccination program on December 19, 2020. After eight months it is seeing a reversal of its early successes as the Delta variant spreads. The U.S. has an even lower vaccination rate than Israel and we are experiencing our own Delta surge wreaking its worst damage in the unvaccinated. With this unfolding reality, how can we still be clinging to our expectation of achieving herd immunity?

For people with compromised immune systems, boosters will be crucial. But even booster vaccinations have limited value in the immunocompromised population. All working immune systems have limitations and cannot function at a state of maximal stimulation continuously. As such, the immune response in immunocompromised individuals will weaken even faster. This will, in turn, make that individual less resistant to infection and more likely to succumb.  What this means is high-risk groups will become even more vulnerable as their immune systems wear out. 

An inescapable conclusion is that vaccines alone are not an effective Covid-19 strategy. Therapeutics are needed. We now have a brief window of opportunity to identify and stockpile effective therapeutics. Even as we continue to strive for greater vaccination compliance, we must redouble our efforts to make therapeutics to treat the damaging effects of Covid-19 available, no matter how the virus evolves. The sooner we recognize and address this need, the sooner we will be able to direct our future. Failure to do so will condemn us to a never-ending cycle of chasing a shape-shifting pathogen.

Dealing with SARS-CoV-2 will also require a long-term commitment to care for those with the long-term effects of the disease (Long Covid). Survival from acute SARS-CoV-2 is not synonymous with cure. The Lancet recently published a study of over 80,000 Covid-19 patients. Of those who survived, 26.6% were less able to care for themselves than before their illness. This disability increased with age, male sex, and in those who received critical care support (such as mechanical ventilation). Having a complication (acute kidney, complex respiratory, and systemic complications are the top three) was independently associated with an increased risk of worse ability to self-care after discharge. Patients who developed neurological complications, though smaller in number, had the strongest associations with worse functional outcome.

Our already overtaxed and overburdened health care systems will be called upon to treat and care for a new population of chronic Post-COVID patients whose numbers will run in the millions. It is late, but not too late, to plan for addressing this scenario.  At a minimum we will require increased staffing and equipment with follow-up facilities to provide treatment and care, and to continue collecting data from these individuals to determine whether these continuing effects are transient or, sadly, permanent.

We must acknowledge the need for a multi-tiered approach, utilizing both vaccines and therapeutics to prevent death, mitigate illness, and treat the long-term physical and financial effects of this pandemic.