‘Killer’ immune cells still recognize Omicron variant.... oh really?
We keep being flooded with exciting news about the magic contribution of T cells to preventing disease or avoiding progression to severe disease (https://www.nature.com/articles/d41586-022-00063-0: ‘Killer’ immune cells still recognize Omicron variant). Given the caliber and reputation of the scientists authoring these publications, one would almost end up believing that T cells are, indeed, doing the trick! However, the interpretation of these data is highly questionable. There is now a plethora of publications that strongly suggest a potential role of SARS-CoV-2-reactive memory T cells in abrogating SARS-CoV-2 infection and preventing Covid-19 disease. However, the authors of these papers don’t seem to feel the need for distinguishing between T cell-mediated cross-reactivity / cross recognition and cross-protection. There is no proof, however, that cross-reactive SARS-CoV-2 memory T cells can abrogate infection and prevent Covid-19 disease1. Even though stimulation of SARS-CoV-2-reactive T memory cells correlates with protection from Covid-19 disease, correlation does not imply causation and it is, indeed, more reasonable to assume that cross-reactive T cell responses directed at SARS-CoV-2-derived proteins / peptides are rather the consequence than the cause of control of infection 2.
Although it seems plausible that cross-reactive T cells (originating from exposure to previous SARS-CoV-2 variants or other CoVs) may prevent progression to severe disease and hence, prevent hospitalization, this has not been unambiguously proven either. Again, correlation does not imply causation: Resistance of Omicron to neutralizing vaccinal antibodies (Abs) restores the functional capacity of the innate line of immune defense and likely explains protection in vaccinees. As already discussed, not T cell immunity but innate, CoV-reactive immunity has the capacity to abrogate infection and hence, to protect against (severe) disease. As innate immunity can also be trained upon repeated exposure (pandemic!), innate immune effector cells continue to play a critical role even in older age groups. It is, therefore, unlikely that protection against Omicron in vaccinees is vaccine-mediated. Consequently, the conclusion that the efficacy of the vaccine against severe disease is not affected by Omicron doesn’t seem right to me.
Based on all of the above, it is reasonable to assume that lower rates of hospitalization in unvaccinated as compared to vaccinated individuals are not due to T cell-mediated protection but to the immune suppressive impact of high infection rates on relevant innate immune Abs in unvaccinated individuals who’ve been re exposed shortly after previous infection (however, there is now increasing evidence that the opposite applies in that Omicron causes higher rates of hospitalization in the vaccinated than in the unvaccinated!).
Many of the scientists who are now claiming a protective role of CoV-reactive T cell epitopes and are even advocating for the inclusion of cross-reactive T cell epitopes in new Covid-19 vaccines are the same who used to shout from the rooftops that T cell based vaccines would protect against HIV, TB, Malaria and many other chronic infectious diseases. However, they never delivered on those goals. Now, they are trying to make us believe that T cell epitopes contribute to vaccine efficacy against SARS-CoV-2 and that we should, therefore, include more of these epitopes in future Covid-19 vaccines! Their interpretation completely ignores the critical role of innate immunity in fighting CoVs and that any additional inclusion of cross-reactive T cell epitopes may even be at risk of inducing immune pathology. It can, indeed, not be ruled out that vaccine-mediated recall of cross-reactive CD4+ T memory cells, for example, promotes immune pathology in a subset of genetically predisposed individuals. Isn’t it surprising that several of these research groups are obtaining direct funding from vaccine companies that are heavily engaged in the ongoing mass vaccination campaigns?
The erroneous interpretation of the role of cross-reactive, CoV-specific T memory cell as a key contributor to the protection of vaccinees from (severe) Covid-19 disease is only grist to the mill of those who can’t see the critical role of our first line of immune defense against CoVs as they are blinded by their addiction to mass vaccination campaigns.