Vaccination is based on the concept of immune memory. When we encounter a new pathogen, we mount an immune response that helps us recover from the infection and also creates immune memory. This process typically takes 1-2 weeks to develop, so we often get sick before there is sufficient immunity to rid our bodies of the new pathogen. Once we recover, the immune memory persists for many years to decades, though it can dwindle with time. If we encounter that same pathogen later on, immune memory allows immediate reactivation of the immune response rather than taking the 1-2 weeks as on initial infection. Because this memory response is so rapid, we rarely get sick on subsequent exposures as the immune response stops the pathogen before it reproduces enough to cause disease.
Vaccinations attempt to mimic pathogen exposure and elicit the memory immune response without causing disease. There are three main types of vaccines: live attenuated virus vaccines, inactivated or “killed” virus vaccines, and subunit vaccines. Live attenuated virus vaccines use a weakened form of the virus that can still infect and may even cause mild symptoms, but isn’t able to elicit the full-fledged disease. The childhood chickenpox vaccine is an example of a live attenuated vaccine. Live vaccines are highly effective because the virus actually replicates to low levels in the vaccinated individual evoking a very robust and long-lived immune response. Unfortunately, live vaccines may cause some mild though uncomfortable disease symptoms in some people. They also can’t be used in immunocompromised individuals or pregnant women, and there is a very rare risk that the attenuated virus might revert to full virulence and cause severe disease. In contrast, inactivated virus vaccines use the whole virus and treat it so that it can no longer replicate and cause disease. The individual virus particles are still intact, just “killed”. Because the injected virus is already “dead” there is no risk of infection with this type of vaccine and it can be used on anyone. Fortunately, when injected into someone, even though it can’t replicate, the killed viruses will elicit neutralizing antibodies and immune memory. Neutralizing antibodies encoat viruses which renders them harmless and prevents infection. However, since this approach doesn’t elicit as robust or long-lasting immunity as live vaccines it may require multiple injections and/or periodic booster shots to keep immunity high. For example, the hepatitis A vaccine is an inactivated vaccine that requires two shots to gain full immunity. Lastly, subunit vaccines consist of only a portion of the virus, usually a surface protein that can be recognized by our immune systems. Both the hepatitis B virus (HBV) and the human papillomavirus (HPV) vaccines are subunit vaccines. Like the killed vaccines, subunit vaccines elicit neutralizing antibodies and immune memory. Subunit vaccines are also quite safe as they cannot cause viral disease since there is no virus present, only a protein.
In the race to find a vaccine for SARS-CoV-2 which causes the COVID-19 disease, many approaches are being explored. Over 100 candidate vaccines are in development, most involving either an inactivated virus or a subunit vaccine. Moderna and the University of Oxford in the United Kingdom are the current frontrunners in this race, both targeting the spike protein on the viral surface. Moderna’s vaccine consists of mRNA that encodes the spike protein contained within lipid nanoparticles. When injected into the arm, the loaded nanoparticles are taken up by cells and the mRNA is translated into the spike protein by the cell’s ribosomes. Early results show the vaccine recipients develop neutralizing antibodies against the spike protein which is a good sign that the vaccine would protect against SARS-CoV-2 infection. The Oxford vaccine uses a different approach and puts the gene for the spike protein into a chimpanzee adenovirus delivery vehicle. Like the Moderna approach, when this monkey virus carrying the spike protein gene is injected into the arm, the recipient should produce the spike protein in their cells and develop neutralizing antibodies. In a challenge study, 6 macaque monkeys who received the Oxford vaccine did not get sick when given SARS-CoV-2. Both the Moderna and Oxford vaccines are already in early human trials so there should be human efficacy results by the end of this year. It’s still too early to predict if either or both vaccines will be the panacea we need, but at least the early science is promising and there are lots of other candidates if the frontrunners falter.