COVID-19 - We Got the Shot. Now What?
Over the last year, the pandemic caused by the SARS‑CoV‑2 virus has devastated economies and resulted in tremendous individual suffering and loss of life. Fortunately, in the recent past effective vaccines and vaccination programs have resulted in control of viral epidemics - with the exception of HIV. The development of vaccines for this virus started with the publication of the viral genome in January 2020. The subsequent course - from laboratory design to phase 3 studies and emergency use authorisation with initiation of vaccine programs - truly occurred at “warp speed”.
However, this development did not occur in isolation. Several viral epidemics occurred in this century, including H1N1 influenza, Ebola, Zika and the other coronavirus infections, SARS and MERS. The vaccine development for the SARS and MERS was interrupted by rapid control of the epidemics. Similar interruptions occurred with the development of Ebola vaccines but following the 2013-2016 Ebola outbreak, research proceeded and resulted in an effective vaccine that was available for the most recent outbreaks.
The requirement of vaccine development for these viruses prompted research into novel ways of producing vaccines that would elicit a robust immune response. In addition, awareness and concern about the potential for a future global pandemic led organisations - such as the Coalition for Epidemic Preparedness Innovations (CEPI) - to support the development of platform technologies to prepare for “Disease X,” which is defined as a newly emerging epidemic disease (such as COVID‑19).
One advantage of the early attempts to develop a vaccine for SARS and MERS was the identification of the spike protein on the viral surface as the most likely effective target for an immune response. (Spike proteins are named for the protrusions on the outside of coronaviruses that help them infect cells.) At the time of writing, there are eight approved vaccines and five vaccines which have been authorised in early or limited use.
At present vaccines in clinical use fall into one of four major categories.
- The first is an inactivated virus, seen in vaccines from China that include Sinopharm and Sinovac.
- The second, a novel approach taken by Pfizer-BioNtech and Moderna, has been to insert into nanoparticles the messenger RNA that “codes for” the spike protein. The RNA induces the host cell to produce the spike protein on the cell surface, which stimulates an immune response.
- The third technique is to purify the spike protein in a cell culture that, when taken up by cells, is expressed on their surface to generate the immune response. Novavax is the approved vaccine in this group.
- The final approach - seen in AstraZeneca, Johnson & Johnson and in Gamaleya’s Sputnik V vaccines - is to take another harmless virus and to modify it to express the SARS‑CoV‑2 spike protein.
The early and encouraging results from the phase 3 trials of the Pfizer-BioNtech vaccine confirmed that the spike protein was an appropriate target and predicted that many of the other vaccines would also have a good protective effect. The results of many trials have been released, prompting emergency use authorisation for several vaccines that have come into clinical practice. Countries have launched “jabbing” programs with varying degrees of efficiency and success, often dictated by the access to vaccines. Predictably, the wealthier countries with more advanced healthcare systems have been most active, but even they have squabbled over vaccine access.
With vaccine rollouts has come the predictable concern about not only the efficacy but also the safety of the vaccines. Initial trials had indicated a good safety profile, and this has been confirmed in the post rollout surveillance programs. Two of the viral vector vaccines have had reports of platelet abnormalities and clotting of the cerebral venous sinus in a small number of recipients. Investigation of this suggests that even if this is a vaccine-related side effect, the incidence is extremely low and the risk of adverse events from contracting COVID‑19 is far higher. The use of these vaccines has continued but with recommendations to use alternatives in young people who would be at very low risk of adverse outcomes from COVID‑19.
Many questions remain but evolving evidence suggests that vaccines will play a major role in achieving herd immunity and controlling this pandemic. The incidence of clinical (and severe) disease is very low among fully vaccinated individuals; population mortality drops dramatically, and those who are infected do appear to be less likely to transmit the disease. Complicating the story is the emergence of viral variants, some of which, such as the “South African” B.1.351 variant, appear to have less sensitivity to the protective effects of some of the vaccines. Vaccine development is responding to this in several ways and it is likely that over the next few years booster or follow‑up vaccines may be required.
How rapidly control of the pandemic is achieved will depend on factors such as the efficiency of the vaccine programmes, adherence to social distancing and wearing of masks to reduce transmission. There is concern that, having had the vaccine, people (particularly the young) will modify this behaviour. It is a global pandemic and requires a global response with support for vaccination programs in Africa and other areas with challenged healthcare systems and limited resources.
There is light at the end of the tunnel, but we are still in the tunnel. Only a small percentage of the world population has been vaccinated. There are emerging variants. Further waves can be expected as variants emerge and travel restrictions are lifted. While we can hope that an effective oral anti-viral medication may become available to attenuate the disease, we should expect that this virus will continue to have an impact on our lives for a number of years and sensible precautions to avoid infection should continue as we transition back into “normal” life.