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By Dr.Sudhir Gupta

Neutralizing antibodies have been primary focus for the protection from serious disease and death from COVID-19, and effectiveness of various vaccines.  Neutralizing antibodies are also tested for their effectiveness against emerging mutant strains of SARS-CoV-2 (Coronavirus), the virus that causes COVID-19 disease. These variants might be partially resistant to antibodies. However, very little attention has been paid to T cells, especially “killer” CD8+ T cells.  Unlike antibodies T cells do not prevent infection because they get into action only after a virus has infiltrated the body; however, they are important in for ongoing infection. Therefore, in case of COVID-19 killer T cells could mean the difference between mild infection and a severe infection that requires hospitalization and death. These Killer T cells recognize viruses and kill viruses-infected cells.  Since viruses require cells they infection for their survival and multiplication, Killer T cells may eliminate cellular factories for coronavirus. The evidence for an important role of T cells in defense against coronavirus comes from patients that are born with genetic defects of the immune system with failure to make any antibodies, including antibodies against coronavirus.  An international study in which we participated, and other studies by us and others of patients with primary antibody deficiency diseases with genetic defects of the immune system who contract coronavirus infection and did not make antibodies against coronavirus had either a mild disease and did not require hospitalization; those required hospitalization recovered from COVID-19.  There was no deaths if they did not any other comorbid conditions. Many of these patients have no B cells to produce antibodies.  If antibodies were critical, we would have expected these patients to have serious COVID-19 and many deaths. Therefore, even though we may not produce antibodies, T cells especially “Killer” T cells may keep us alive. The role of T cells may also be important when we consider different vaccine, especially against mutant strains.  However, before we consider vaccine, we should consider few facts about mutations. RNA viruses are very prone to mutations, therefore, mutations in SARS-CoV-2 should not come as a surprise. When viruses mutate they change their characteristics, they could become more transmissible (infectious) but not pathogenic (disease causing), or they may nor change transmissibility but become more pathogenic, or they may become more infectious and more pathogenic.  SARS-CoV-2 mutations (UK, Brazil, South Africa) have shown to be more infectious; however, limited data on the pathogenicity. In a recent study, researcher has shown that that South African mutants (B.1.351) were partially resistant to antibodies raised against various coronaviruses; however, T cells were active against this variant because T cells did not target region of virus that were mutated. All except one (COVEXIN) vaccine are targeting spike protein, where majority of mutations occur, including against receptor binding domain (RBD). Therefore, vaccine that are targeted against spike protein may not be fully effective against mutant strains. However, vaccine using the inactivated whole virus (COVAXIN) is likely to elicit both antibody and T cell responses against all components of the virus including membrane, envelope, and nucleocapsid proteins. Therefore, in mutated strains of virus, killer T cell should be able to recognized non-mutated components of the virus and kill virus infected cells, and clear the infection.

We should also remember a basic difference between ‘natural immunity’ that is acquired following an infection and “vaccine-induced” immunity. Whereas natural infection induces “sterile” immunity, vaccine induces “protective immunity”.  In case of COVID-19, virus infections starts from mouth, nose, upper respiratory tract, where major protective antibodies are IgA, whereas in lower respiratory tract and lung, major protective antibodies are IgG.  Intramuscular vaccination induces a systemic response predominantly of IgG antibodies, therefore, vaccinated individual may still contract infection and transmit infection, but may not have serious disease. Therefore, we should continue to wear mask even after receiving vaccine until we have reached “herd” immunity.  How long the immunity would last from natural infection versus vaccine requires further study of both memory antibody producing B cells and effector memory T cells.

The writer is Dr.Sudhir Gupta, Professor of Medicine, Microbiology & Molecular Genetics, University of California, Irvine, USA.