by Paul Bieniasz
Dr. Bieniasz is Professor and Investigator of the Howard Hughes Medical Institute at Rockefeller University.
As viruses go, SARS-CoV-2, is quite easy to neutralize with antibodies and, it turns out, straightforward to generate effective vaccines based on the spike protein. Perhaps, even probably, those two properties are causally related. Moreover, it appears that it is quite hard (albeit not impossible) to generate resistant spike variants that evade the polyclonal antibody responses elicited by said vaccines. This is all excellent news.
However, if I had a nefarious nature and wanted to ensure that the new SARS-CoV-2 vaccines were rendered impotent, these are a few things I would try.
First, we’d want to maximize the viral population size and diversity. Because SARS-CoV-2 has a proofreading polymerase, we might have to work hard to do this. The four measures outlined below might help accomplish this, assisting the virus to explore as much genetic diversity as possible, generating every conceivable point mutation as frequently as possible.
- Delay the rollout of testing, so that the virus could spread undetected, seeding outbreaks in geographically, demographically and culturally diverse host populations, rendering it virtually impossible to quash with test-trace-isolate approaches.
- Implement partial and patchy restrictions on movement and social interactions, thus maintaining consistently large pools of infected individuals.
- Keep schools open, claiming that children don’t frequently transmit SARS-CoV-2. Because children have generally mild and perhaps more frequently asymptomatic infections, diversifying viral populations are more likely to spread undetected.
- Start a rumor-mill, making full use of social media and other outlets, with topics such as masks are unnecessary or don’t work, that PCR tests are too sensitive or unreliable, that infection-induced ‘herd immunity’ is a reasonable strategy, or even that SARS-CoV-2 isn’t real. Undermining already inadequate public health measures helps keep viral population sizes large.
Second, during or after the establishment of large and diverse viral populations, we’d begin to apply selection pressure to enrich antibody resistance mutations. For that, we would elicit the help of the medical establishment to implement measures 5 and 6. They, laudably, want to help as many people as possible as quickly as possible — we could exploit this.
- Treat tens of thousands of people with uncharacterized convalescent plasma of weak/unknown potency, without proper clinical trials, to get the ball rolling in applying some selection pressure to enrich for antibody resistant variants. (Again, I don’t know how effective this would be since it is mostly done in hospitals, where onward transmission would presumably be rare, but it would certainly be worth a try) Immunocompromised individuals with persistent infection might be especially helpful here.
- Finally, and here’s the kicker: having developed a remarkable two-dose vaccine, that is extraordinarily effective, ADMINISTER IT TO MILLIONS OF PEOPLE – BUT DELAY THE SECOND DOSE. Generating a pool of hosts with just the right amount of neutralizing antibody to apply selection pressure, but also maintain sufficient levels of partially antibody-resistant virus to allow onward transmission is key here. We might not achieve this shortly after the first dose, but if we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot.
Of course, I don’t know if the above would be successful, but that’s what I’d try if I wanted to generate vaccine-resistant SARS-CoV-2 variants.