The Risk of Immune Escape

Last week, I pointed, for the first time, to my concern about the risk of immune (or immunological, or antigenic) escape by one of the new SARS-CoV-2 variants. My concern was triggered by this podcast episode from the NEJM, and in response to my inquiry, one of the NEJM editors who has been kind enough to correspond with me via email from time to time wrote: “I think that it’s just too early [to know about the risk of immune escape]. […] But we should know fairly soon, particularly if we see cases in vaccinated individuals. There will also be in vitro data about antibody binding (some of which is already in the media) but we don’t know the significance of this yet.”

To the point about antibody binding, this Nature article from January 7th of this year concludes, “There is emerging evidence that the E484K mutation can enable the virus to escape some people’s immune responses. […] But […] scientists are hopeful that the mutations in the variants won’t substantially weaken the performance of vaccines.” The article also points, however, to a recent pre-print [that is, an as-yet-un-peer-reviewed publication] that suggests: “The evolution of SARS-CoV-2 could impair recognition of the virus by human antibody-mediated immunity.” If both the former hope and the latter possibility prove true, it would mean that new variants with this mutation (chief among them, for now, the 501Y.V2 variant that was first identified in South Africa) might prove resistant to immunity inferred by infection with older SARS-CoV-2 variants, but still subject to immunity conferred by vaccines. This would be good news, in a measured sense, but would militate against my bull case for the pandemic ending in the spring in the US, given that it could mean that many of us who already had COVID-19 might not enjoy any naturally conferred protection against the new variant(s).

This piece from the 15th (from Science, but journalistic in tone) quotes a researcher as follows: “Several vaccines could be easily changed to reflect the latest changes, but regulators might balk at authorizing them without seeing updated safety and efficacy data,” while this pre-print [again, not yet peer reviewed] from the 13th offers the most alarming assessment: “Rapidly spreading SARS-CoV-2 variants present not only an increased threat to human health due to the confirmed greater transmissibility of several of these new strains but, due to conformational changes induced by the mutations, may render first-wave SARS-CoV-2 convalescent sera, vaccine-induced antibodies, or recombinant neutralizing antibodies […] ineffective.”

Finally, this BMJ piece from today offers a helpful summary of the three most worrying variants (B.1.1.7, first identified in the UK; 501Y.V2, first identified in South Africa; and P.1, first identified in Brazil), and, among other things, quotes a researcher as follows: “[T]he variants may be arising in Brazil and South Africa because of high transmission (as many as 40-50% of people being infected) in populations living in crowded conditions.” It would be the height of brutal irony if failures to take public health seriously globally – failures epitomized by vaccine nationalism and the collapse of many multilateral programs once spearheaded by the US, and characterized by a lack of concern about the lives and well-being of the poor, especially across the Global South – undermined the efficacy of vaccines just at the moment when the US and other rich countries across the Global North – having mostly failed to control COVID-19 through well-understood non-pharmaceutical interventions – are rushing headlong towards what they hoped would be the techno-medical denouement of the(ir) pandemic.

We should care about public health globally because people’s lives matter, but I fear that even the hard-hearted (who so often see themselves as cold-blooded pragmatists) may be on the verge of learning a painful lesson about the consequences of embracing parochial (and inhumane) solutions to complex problems.