It is our wits against their genes.” This succinct observation of Joshua Lederberg on microbes was published in the journal Science in 2000. Lederberg was very well qualified to make this comment. He had won the Nobel Prize for Medicine in 1958 for his pioneering work on microbial genetics. He also cautioned against using war like metaphors such as ‘eradication’ loosely against the microbes, reminding us that most microbes will coexist with us in an ecological balance.
In establishing such a relationship, microbes are propelled by ecological and evolutionary forces. Ecological changes bring them into contact with human species when deforestation brings forest-dwelling microbes into contact with humans, directly or via an intermediate animal host. The ability of the microbial species to survive subsequently depends on its ability to evolve to a state where it can continue to infect a host species but does not wipe it out. To be so virulent as to eliminate the host species would be a dead end for the microbe. Humans will fight the microbe with their immunological response, vaccines and drugs. The much larger human body evolves very slowly, while the minuscule microbial species evolves very rapidly. So microbial mutations mostly set the pace for determining the nature of our coexistence.
Microbial mutations can occur through ‘antigenic drift’ or ‘antigenic shift’. Antigenic drift is when a virus has mutations in its proteins that make it partially resistant to the immune mechanisms that have developed in a human population. Antigenic shift is more threatening, as two or more viruses exchange their genetic material to create a new entity that is totally unfamiliar to the body’s immune system.
In the past three months, global alarm has mounted over variants reported from mutants of the SARS-CoV2 virus that have a more infectious character than the previously prevalent version. They represent the products of antigenic drift, developed under the evolutionary pressure of lockdowns, masks, physical distancing and vaccines that are slowing down the spread of the virus. At least one of them, from South Africa, has been found to substantially reduce the efficacy of vaccines in preventing infections, amounting to ‘vaccine escape’.
The mutations have been mainly in the ‘spike protein’ of the virus. This appears as crown-like spikes on the surface of the coronavirus. These spikes are used by the virus to attach to ACE2 receptors on the surface of human cells and then prise open the entry into the cell. The mutations are aimed at making the attachment and entry easier. Mutants can also arise by mistakes committed when the virus uses host genetic material to make its copies. The RNA viruses do not have the mechanism to ‘edit’ those mistakes. So the viruses keep making mutants, some of which are useful for propagation and preservation of the species and others that soon fade away as they confer no evolutionary advantage.
Several mutants of the SARS-CoV2 virus have emerged over the past 14 months. Most of them did not attract public attention, appearing as mere extras in the crowd scene of the pandemic. A few others have risen to stardom, with greater infectivity to grab more screen time and some even displaying the audacity of staging a ‘vaccine escape’ to create more dread. Their names are complicated, with alphabets and numerals indicating the site of the mutation, the original amino acid and the substituted amino acid. Despite the scientific recommendation to avoid pejoratively linking the mutant with a country or province, the given codes are not easy to report in the media. Hence people still refer by the name of the place where they were first reported.
The first to hit the headlines was B1.1.7 (UK-Kent), which was reported to have a 70% higher infectivity rate. Though higher virulence too was suggested later, there is no clear evidence of that. The next was B.1.351 (South Africa), which was reported to be not only more infectious but also less vulnerable to vaccine induced immunity. P.1, reported from Brazil, also shares a mutation at E.484.K location with the South African variant. Apart from a low efficacy rate reported for the AstraZeneca vaccine against the mutant reported from South Africa, even the J&J vaccine has shown lower efficacy in South Africa and Latin America than in the US in the trial. The Novavax trial too reported 49% efficacy against the South African variant, contrasting with 89% efficacy in the UK.
Some of the vaccine platforms, such as the mRNA vaccines, can be tweaked, in six-eight weeks, to adapt the immune response to the variants that have been detected. It is also possible that vaccines that are not limited to the spike protein antigen and offer more antigens of the virus as targets for the immune response may fare well against the mutants that rely on spike protein changes. Inactivated virus vaccines belong to this group. Even as we await the vaccines to adapt their antigens, to mount a stronger defence against the variants, we must recognise that the primary protection comes from preventing the infection itself. Whatever the mutation, masks, hand washing, physical distancing and ventilation will prevent viral entry into the body.
Indeed, it is our wits that we must depend on to overcome the microbes, even as their genes play tricks on us by masquerading as mutants.
(Dr Reddy is the author of ‘Make Health in India: Reaching a Billion Plus’. Views are personal)
(ksrinath.reddy@phfi.org)
Dr K Srinath Reddy
Cardiologist, epidemiologist & President, Public Health Foundation of India (PHFI)