Neutralising antibodies have been a primary focus for the protection from serious disease and death from Covid-19, and the 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. 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 but they are important for ongoing infection. Therefore, in the case of Covid-19 killer T cells could mean the difference between mild infection and a severe infection that requires hospitalisation and death. These killer T cells recognise viruses and kill viruses-infected cells. Since viruses require cells for their survival and multiplication, killer T cells may eliminate cellular factories for coronavirus. The evidence for an important role of T cells in defence against coronavirus comes from patients who 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 hospitalisation and those who required hospitalisation recovered from Covid-19. There were no deaths if they did not have 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 vaccines, especially against mutant strains. However, before we consider the vaccine, we should consider a few facts about mutations. RNA viruses are very prone to mutations so 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 not 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, there is limited data on the pathogenicity.
In a recent study, a researcher has shown 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 the region of the virus that were mutated. All except one (COVAXIN) vaccine are targeting spike protein where the majority of mutations occur including against receptor-binding domain (RBD). Therefore, a vaccine that is targeted against spike protein may not be fully effective against mutant strains. However, a 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 the virus, the killer T cell should be able to recognise non-mutated components of the virus, kill virus-infected cells and clear the infection.
We should also remember a basic difference between ‘natural immunity’ that is acquired after infection and ‘vaccine-induced’ immunity. Natural infection induces “sterile” immunity, whereas vaccine induces “protective immunity”. In the case of Covid-19, virus infections start from the mouth, nose, and upper respiratory tract where major protective antibodies are Immunoglobulin A (IgA), whereas in the lower respiratory tract and lung, major protective antibodies are Immunoglobulin G (IgG). Intramuscular vaccination induces a systemic response predominantly of IgG antibodies. Therefore, a vaccinated individual may still contract and transmit the infection but may not have a serious disease. Hence, we should continue to wear a mask even after receiving the 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 a professor of medicine, microbiology, and molecular genetics, the University of California, Irvine, USA.
