SARS-CoV2 vaccines: Slow is fast

..The need to develop a vaccine is urgent, but most estimates conclude that even if trials are successful, an effective vaccine will not be widely available for 12 to 18 months. Much of the required time is related to the pace of proper clinical trials. Studies are usually first needed in experimental animals. However, non-human primates rarely display severe symptoms, and critical disease is also not observed in other species, including genetically engineered mice..

..There are potential reasons why an immune response to a vaccine can predispose an individual to a worse outcome upon infection. One is the phenomenon of antibody-dependent enhancement (ADE). In this effect, antibodies that bind to the virus also bind to antibody receptors on cells, facilitating uptake and infection of the cell bearing the receptors. ADE has been observed for vaccines against Dengue, Ebola, and HIV (4). As recently as 2017, a large-scale efficacy trial of a Dengue vaccine resulted in ADE in vaccinated children (5). Troublingly, ADE has also been seen with vaccines for a feline coronavirus (6, 7). There is also evidence for ADE in SARS-CoV. Studies have shown that rodent and human antibodies to the S protein can enhance infection in vitro (8–11). However, several small preclinical studies of a SARS-CoV vaccine in rhesus monkeys failed to observe evidence of ADE.

One SARS-CoV2 vaccine, employing inactivated virus, was tested in several large cohorts of rhesus monkeys, with substantial efficacy and no evidence of ADE (12). While this is clearly encouraging, the need to ensure that any vaccine is, indeed, safe is of vital importance.

While there is a need for caution, the need for accelerating testing is clear, and many discussions are occurring on how to ethically perform experimental infection studies in humans. Such studies provide enormous progress in vaccine research, but of course the extreme risks must be weighed against potential benefits. The same applies to the ultimate use of a vaccine that shows adverse effects in clinical testing.

Referring to experimental research, the eminent cancer biologist, Charles Sherr once told me, “Fast is slow, and slow is fast.” This is a maxim that must be applied to vaccine development for COVID-19