Now that COVID vaccines have established mRNA technology as the “new frontier for vaccine development,” pharma giants have set their sights on an mRNA vaccine for respiratory syncytial virus (RSV) — which they hope to add to an already overburdened childhood vaccine schedule.
That lesson, in the words of Harvard medical historian David Jones, is that “when it comes to vaccines and immunization … there always has been a risk and there always will be a risk.”
Sixty-five years ago, families learned about the risks of medical experimentation the hard way when they allowed researchers to use their infants as test subjects for a vaccine against a newly discovered illness dubbed “respiratory syncytial virus” (RSV), a common-cold-like illness now considered to affect “virtually all children,” mostly uneventfully, by age two.
Since that time, vexed researchers have continued to deploy “trial-and-error approaches.” But they admit the “road to an effective RSV vaccine is paved with challenges,” in large part because of the tricky problem of “vaccine-associated disease exacerbation” — a problem that has also plagued coronavirus vaccines.
The gist of the “exacerbation” issue, also called antibody-dependent enhancement or pathogenic priming, is that the vaccine “primes” recipients to later develop more severe disease instead of protecting them.
Lured by the prospect of a large untapped global RSV vaccine market, manufacturers are nonetheless setting their sights on RSV vaccine development — and not just for infants but also for pregnant women and the elderly.
By 2019, capitalizing on the proliferation of new vaccine technologies, clinical trials were evaluating an estimated 30 candidate RSV vaccines, and scientists were gleefully announcing that the world “might be on the brink of clinical implementation soon.”
The crowded field of RSV vaccine candidates includes messenger RNA (mRNA) vaccines. In fact, with COVID injections having opened the floodgates to establish mRNA technology as the “new frontier for vaccine development,” pharma giants appear more confident than ever that they are close to finally producing an RSV winner.
In a nod to these hopes, the U.S. Food and Drug Administration (FDA) has just granted fast-track designation to Moderna for the company’s experimental mRNA-1345 vaccine against RSV. Although the fast-track FDA review applies only to older adults for now, Moderna’s phase 1 trials of its RSV injection also include children as young as 1 year old.
What about safety?
The 1960s RSV vaccine was a disaster in terms of safety, but researchers engaged in subsequent RSV vaccine attempts have tried to steer public attention away from risks and toward a single-minded focus on effectiveness.
With the help of industry-standard study design tricks — such as monitoring adverse events for only a short while or comparing the vaccine against immune-activating aluminum adjuvants or other vaccines (rather than an inert placebo) — manufacturers have managed to keep potential safety problems in the shadows.
The foundational ethical standards underpinning research on human subjects demand special attention to vulnerable populations, including fetuses, neonates, pregnant women and the institutionalized elderly.
Yet these are precisely the populations that RSV studies have targeted — all flops, with none leading to a licensed vaccine and a bare minimum of disclosure about safety.