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10 March, 2021

How Covid-19 Vaccines Work and Future Lessons for Vaccination

Gary McDowell, PhD, University of Cambridge

Zachary Marcus, MD, MPhil, University of Cambridge

Covid19 Vaccines

One year after countries around the world began to lock down and restrict travel in response to the COVID-19 pandemic, multiple highly effective vaccines have been developed and are being administered to people. With some nations now anticipating a more normal summer, it’s important to consider this remarkable scientific achievement and what it means for the future. Here we describe how the vaccines were developed; how they work; what we may expect for COVID-19 vaccination in the future; and implications for a post-COVID world.

How were the vaccines developed so quickly?

The speed with which multiple COVID-19 vaccines were developed was impressive, and there are a number of factors that contributed to this success, including a recent focus on vaccine research; swift and substantial funding for vaccine research; and prioritization of the vaccines by regulatory authorities (Ball, 2020). Vaccine research and development, and improvements into manufacturing processes, have been areas of interest due to recent epidemics and pandemics, particularly the SARS epidemic of 2003 (related to SARS-Cov-2, the virus that causes COVID-19). Great strides have been made in recent years in developing RNA vaccines to treat cancer (Dolgin, 2019). Already-existing efforts to address the impending threat of a pandemic (such as the formation of the Coalition for Epidemic Preparedness Innovations) combined with the acute political, economic, and societal interests in resolving lockdown measures have led to the acceleration of vaccine development and use. In the US, the Federal Drug Administration’s Emergency Use Order (FDA, 2020) has allowed speedy roll out of these vaccines after evaluating them for safety and effectiveness.


How do the vaccines work?

Vaccines work by teaching the immune system to recognize and “remember” part of a disease causing bacteria or virus. When a vaccinated person is later exposed to the actual bacteria or virus, the immune system can address and neutralize the infection more quickly and effectively - most times with the person showing no or few symptoms of disease.


There are different ways of “teaching” the immune system. Currently there are COVID-19 vaccines that work as vector vaccines (such as the Johnson & Johnson vaccine) and mRNA vaccines (such as the Pfizer-BioNTech and Moderna vaccines). Protein subunit vaccines are likely to emerge soon (Blackney and McKay, 2021). The Pfizer-BioNTech and Moderna vaccines are the first readily available mRNA vaccines, although the technology that makes them possible has been researched and developed for decades (Komaroff, 2020).


Viral vector vaccines use a virus that is harmless to humans to deliver a piece of the concerning virus’s genetic material into human cells thereby causing the cell to produce and place a corresponding protein on its surface (CDC, 2021). The body’s immune system recognizes that the protein does not belong and triggers an immune response to fight this phantom infection. mRNA vaccines directly introduce genetic instructions for the body to make the virus protein and subsequently develop the immune response (CDC, 2020). The protein subunit vaccines skip the mRNA step too, and present a harmless part of a COVID-19 protein directly to the immune system (Gavi, 2021). Each of these methods of providing immunity have been demonstrated to be effective. These COVID vaccines do not change human DNA and cannot cause COVID infection.


Outside of the US, other vaccines are currently being used and studied further (Zimmer, Corum and Wee, 2021). These include: Oxford-AstraZeneca, Gamaleya (or “Sputnik”) and CanSino (viral vector vaccines); Vector Institute and Novavax (protein subunit vaccines); and Sinopharm, Sinopharm-Wuhan, Sinovac, and Bharat Biotech (inactivated vaccines). Each type of vaccine in the end has the same goal – to “teach” the immune system to “remember” an infection so when it sees it for the first time it can fight it off.

What does “effectiveness” mean?

All three vaccines (Moderna, Pfizer-BioNTech, and Johnson & Johnson) currently authorized by the FDA in the U.S. were demonstrated to be 100% effective in trials at preventing hospitalizations and death due to COVID-19 infections (Scott, 2021). Where the vaccines differ is in their ability to prevent non-critical cases of the disease. There is currently insufficient data to say for certain how effective current vaccines are when dealing with variants of the virus that have arisen in South Africa, the UK, and Brazil.


COVID-19 Vaccination: Future Developments and Lessons

One of the key difficulties in developing vaccines against viral pathogens is the ability of viruses to mutate rapidly. Variants of COVID-19 have emerged and are circulating, and vaccine researchers are investigating both the need for and development of booster shots to deal with the variants. Just as the flu shot is repeated every year to address annual changes in the influenza virus, there exists the possibility that changes to future COVID vaccines will be necessary to address new variants of the COVID virus.


In recent years, the National Institute of Allergy and Infectious Diseases has been working on developing a universal flu vaccine, with the goal of providing effective immunity against all strains of flu, and avoiding the need for an annual shot (NIAID, 2019). With the recent focus on pandemic preparedness, avoiding another influenza-based pandemic (such as the 2009 H1N1 pandemic) with such a vaccine seems a likely future direction for increased research and development.


The COVID-19 vaccination process has laid bare where some of the strengths in addressing a pandemic lie (e.g. research and development), but also some weaknesses. While the logistical effort of getting vaccines to people has been an impressive undertaking, scaling up the manufacturing process has caused delays, and the scarcity of vaccines has illustrated a global inequity in access to vaccines both among and within countries -- often along racial, ethnic, and socioeconomic lines.


Public health communication has also faced difficulties. Going forward, historical distrust of the medical establishment and vaccine disinformation campaigns will need to be addressed. In particular, it may be necessary to revive lessons learned from other epidemics such as that of HIV/AIDS and pivot away from public health messaging focused on “shaming” and perfect adherence and instead move toward messaging focusing on “harm reduction” (Tufekci, 2021).


Disclaimer: This information is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment.