Coronavirus Vaccines: Two Dose vs. One Dose

Written by: Duke Yuvaraj

Edited by: Sami Morse, Kathleen Navas, Maura McDonagh, & Shayan Hosseinzadeh

On Saturday, Feb. 27, the FDA announced that Johnson and Johnson’s single-dose adenovirus-based SARS-CoV-2 vaccine received Emergency Use Authorization for individuals over the age of 18. As described in our article detailing the Johnson & Johnson vaccine, “The vaccine is a viral vector vaccine, meaning it uses a genetically modulated variant of the common cold virus to carry a SARS-CoV-2 gene to human cells, provoke an immune response against the corresponding SARS-CoV-2 protein, and prime the immune system to fight off later potential infection with the coronavirus.”

Both the Pfizer-BioNTech and Moderna vaccines that were previously approved are administered in a two-dose schedule, and rely upon giving our cells a genetic sequence that encodes the spike protein on the virus’ exterior – thereby exposing our immune system to the spike protein itself. However, the mechanism of the vaccine isn’t what determines the number of doses. So what does?

To explain the differences in doses, first we need to understand that to fulfill its purpose, a vaccine must allow the patient to fight off a viral infection upon exposure–and before symptoms arise. In the case of the SARS-CoV-2 virus, this is accomplished by introducing the body to spike proteins present on the surface of the virus, and allowing them to be recognized by the immune system. Through a process known as “affinity maturation,” B-cells, which are cells involved in the adaptive immune response, can bind the target (spike) with cell-surface antibodies that will proliferate throughout the patient’s body. To clarify, antibodies are generated by the immune system and bind to specific target proteins known as antigens (in this case, the spike protein) – effectively stopping them from entering the body’s cells, and flagging them for other immune response cells to eliminate. So an effective vaccine helps the body generate lots of antibodies against a specific antigen, which allows the immune system to do its job and eliminate the virus.

The key statistic, used to interpret how well a vaccine facilitates the generation of antibodies, is efficacy – how well a vaccine prevents symptomatic disease. Generally, in clinical trials, researchers compare the relative risk between vaccinated and placebo individuals. Efficacy is calculated as a comparison of the number of vaccinated individuals who contracted the disease to the number of unvaccinated individuals who contracted the disease. Against infection, the Pfizer-BioNTech vaccine has an efficacy (in preventing infection) of 46% after the first dose, and is 92% effective a week after the second dose. Furthermore, it has been found that the Pfizer vaccine is 95.3% effective in preventing severe disease, as defined by the U.S. Food and Drug Administration. It’s worth noting that both doses of the mRNA vaccines are identical–the second exposure, or “booster” dose, creates a stronger immune response, which may be partially due to the affinity maturation process, resulting in a larger number of antibodies circulating through the body. In comparison, the Johnson and Johnson vaccine has been found to have a 72% efficacy rate in the United States.

Given the efficacy data of multiple functional vaccines, how should they be distributed?

A 2015 article titled “One versus two doses: What is the best use of vaccine in an influenza pandemic?” uses mathematical models to answer this question. The paper ultimately posits that “a one-dose strategy is optimal if the protection gained after one dose is substantial. A two-doses strategy is optimal if little protection is gained after a single dose.” Since the Johnson and Johnson vaccine has a relatively high protection rate (efficacy) after its first dose, it plays a different role than the two-dose vaccines from a public health perspective. The paper also states that “the optimal use of vaccine[s] probably involves vaccinating high-risk groups with two doses and low-risk ones with a single dose,” which is exactly what is happening today. Phase 1 vaccination of healthcare workers and senior citizens is in progress in California, largely with supplies from Moderna & Pfizer-BioNTech. And with the newly approved Johnson and Johnson vaccine, the scope of people eligible for vaccinations has been expanded.

When comparing vaccines, it is important to understand their purpose in helping the human population without getting lost within the data. Two-dose vaccines elicit higher immunity, making them ideal for at-risk populations such as senior citizens and healthcare workers, while the Johnson and Johnson single-dose vaccine helps the general population reach herd immunity at a faster rate. As the SARS-CoV-2 virus evolves, the speed at which we reach herd immunity becomes more and more pressing, making this vaccine an excellent new tool in the fight against the coronavirus.

Results from ongoing research and the current understanding of COVID-19 are constantly evolving. This post contains information that was last updated on March 31, 2021.

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