Can you explain in general lay terms different vaccine approaches? What are the pros and cons of these different approaches?

By Alan Moy, MD

There are in general 3 types of vaccine approaches: live attenuated virus vaccine, killed virus vaccine and subunit vaccine. A live attenuated vaccine involves using a live virus, which has been artificially weakened (e.g. MMR vaccine). Live attenuated vaccines provide quick and lifelong immunity. The downside is that there is a risk that the attenuated virus could revert to its original wild-type state and cause the infection. A killed viral vaccine (e.g. seasonal influenza) is exactly what it sounds like. A wild-type virus is grown in a cell culture, collected and then killed with a chemical agent (e.g. formalin). Yet, a killed viral vaccine provides a weaker immunity compared to a live attenuated vaccine. A subunit vaccine involves developing immunity against a viral protein, which hopefully will provide immunity against the whole virus. In the case of coronavirus, subunit vaccines typically target the "spike protein" (you have all seen pictures of coronavirus on TV which is shaped as a ball with tiny "spikes" emanating from it). Subunit vaccines provide a weak initial immune response and require multiple boosters over several weeks. Subunit vaccines are not particularly good for first line healthcare responders who need rapid immunity. Subunit vaccine produce viral proteins indirectly by using synthetic nucleic acid (DNA or RNA), which do not require cultured cells; or can be directly synthesized using a cultured cell. Human cell lines are typically preferred to produce viral proteins, but they carry a moral controversy because the only available human cell lines in the past were derived from past abortions. Non-human cells, which are free of moral controversy, can be used but they produce suboptimal vaccines. Subunit vaccines were attempted after the SARS and MERS outbreak but they failed for a variety of technical reasons. The vaccines that are being contemplated for COVID-19 are largely based on a subunit type, but not all are using aborted fetal cells.

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