In an interview for the Human Vaccines Project in September 2022, Kristen Jill Abboud spoke to Professor Deepta Bhattacharya of the University of Arizona Cancer Centre. They explored the relationship between SARS-CoV-2 and immune imprinting and examined the connection between vaccination and variants.  

Omicron antibodies 

The interview begins with a question about the omicron variant, and whether it might be “less immunogenic” after studies demonstrated lower antibody levels after infection. Professor Bhattacharya acknowledges this but wants to examine the “theories” behind it. He suggests that one such theory is that “there is something about the structure of the Spike protein of omicron that makes it harder to make antibodies against”. However, he isn’t “enthralled” by this idea.  

“I think it’s more likely that the immune system makes antibody responses in proportion to how much virus there is and how much inflammation there is.” 

Recalling the start of the pandemic, he contrasts early infections to the “omicron sub-lineages”. These are “making people less sick” on the whole, which he believes is “the most likely explanation” for decreased antibody responses. 

Immune imprinting 

Abboud then asks Professor Bhattacharya to “define” immune imprinting and explain whether he thought it contributed to a “blunted” immune response. Professor Bhattacharya states that it “very simply means” that initial exposure, whether by infection or vaccination, “influences what the immune system does” when it next encounters the virus.  

“Whether that’s a good thing or a bad thing is a different story.”  

He points to a lack of evidence, “none whatsoever”, in fact, to suggest that “prior immune memory hinders the body’s ability to clear the virus. Furthermore, he suggests that “every bit of evidence” shows that it is “helpful to have prior immune memory”. Using the personal example of vaccination before omicron infection, he identifies that the “first immune response” will be “memory cells” that “recognise parts of the virus that haven’t changed”.

His “real question”, therefore, is “whether that response then prevents new responses from being generated” against updated parts of the virus. Although that would be a worrying case, “we’re not seeing any correlation like that”. Thus, the body sems to respond to both “conserved” and “mutated” parts of the virus.  Professor Bhattacharya suggests that it is “tough” to do quantitative studies to assess the extent of immune imprinting. This is because the unvaccinated or “completely immunologically naïve” are a “tough group” to identify.  

What about flu? 

Abboud also asks about patterns with the influenza virus, and whether initial exposure “clearly hinders” later responses. Interestingly, Professor Bhattacharya suggests that epidemiological evidence “implies that birth year has something to do with your relative protection”. However, we still don’t entirely understand the implications of this.  

“Immunologically, it’s been pretty hard to show a detriment from your first exposure.” 

He believes that it’s more that “you generate a disproportionately huge” response to strains that are most like the initial immune encounter.  

Future boosting 

Finally, Abboud asks what the “best strategy” is for “boosting people’s immunity” against COVID. Professor Bhattacharya believes that we will approach it with a “flu mindset”, updating vaccines annually. He suggests that in theory, “one could argue that the vaccines will need to be updated more often than that”, but it won’t happen realistically. Ultimately, he thinks we will “piggyback” COVID boosters on flu rollouts and “do the best we can”. Identifying mucosal and variant-proof vaccines as “very promising”, he doesn’t think it possible to get lasting immunity. However, he hopes it will be possible to “stretch it out” for a few years rather than a few months.  

If you would like to learn more about variant-proof vaccines click here to read about CEPI’s hopes for future vaccines. For more on universal flu vaccines click here. To hear more about COVID-19 vaccination at the World Vaccine Congress in Europe, 2022, get your tickets at this link