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A new, large-scale study finds that mRNA vaccines provide long lasting protection against severe COVID-19. Allen J. Schaben/Getty Images
  • The Pfizer, Moderna, and Johnson & Johnson vaccines gained authorization between December 2020 and February 2021 based on short-term efficacy data from clinical trials.
  • A recent study used data collected from the entire population of North Carolina to assess the long-term effectiveness of these vaccines in preventing SARS-CoV-2 infection, hospitalizations, and deaths.
  • This large study found that the three vaccines, especially the Pfizer and Moderna mRNA vaccines, provided a high degree of protection against severe illness at least 6 months after vaccination.
  • The data suggested that the effectiveness of the vaccines against SARS-CoV-2 infection had an intrinsic tendency to decline gradually after 1-2 months, and the emergence of the Delta variant contributed to a further decline in vaccine effectiveness.

A recent study used surveillance data for the entire population of North Carolina to evaluate the durability of protection provided by the Pfizer, Moderna, and Johnson & Johnson vaccines.

This large observational study showed that all vaccines provided a high degree of protection against hospitalizations and death at least 6 months after vaccination.

However, there was a gradual decline in the ability of these vaccines to prevent SARS-CoV-2 infection following 1-2 months after vaccination, with the lowest level of protection observed in individuals receiving the Johnson & Johnson vaccine.

The study’s first author Dr. Dan-Yu Lin, a professor at the University of North Carolina at Chapel Hill, told Medical News Today, “Many decisions in the United States about COVID-19 vaccination and boosters were based on data from other countries, particularly Israeli data on the Pfizer vaccine.”

“Our study provides a precise and comprehensive characterization of the effectiveness of the three vaccines employed in the U.S. To my knowledge, this is the largest study on vaccine effectiveness, covering more than 10 million people.”

The study appears in the journal New England Journal of Medicine.

The Food and Drug Administration (FDA) granted emergency approval for the use of the two-dose Pfizer and Moderna mRNA vaccines and the single-dose Johnson & Johnson vaccine against COVID-19 between December 2020 and February 2021.

They based the authorization of these vaccines on short-term safety and efficacy data from clinical trials. However, they did not know how long the protection afforded by the three approved COVID-19 vaccines would last.

Moreover, the rise in the number of vaccinated people developing COVID-19 a few months after immunization and the emergence of the Delta variant led to concerns about the durability of protection provided by these vaccines.

Multiple studies have since evaluated the long-term efficiency of these vaccines. These studies have reported a decline in protection a few months after receiving the last dose of the vaccine. However, this period also coincided with the emergence of the Delta variant.

Thus, whether this decline in efficacy of COVID-19 vaccines was due to waning immunity, the emergence of new variants, or both was unclear.

The objective of the present study was to characterize further the durability of protection provided by the three FDA-approved COVID-19 vaccines.

Previous studies have evaluated the effectiveness of vaccines by estimating the cumulative or overall incidence of breakthrough infections over 1-3 months after vaccination. Dr. Lin noted that “Unlike other studies, we estimated the vaccine effectiveness in reducing the current risk of disease as a continuous function of time elapsed since vaccination, as opposed to cumulative incidence over a broad time interval.”

To evaluate the long-term effectiveness of these vaccines, the researchers used data collected by the North Carolina COVID-19 Surveillance System and COVID-19 vaccine management system between December 2020 and September 8, 2021.

The North Carolina Covid-19 Surveillance System collects data on the number of COVID-19 cases and clinical outcomes for COVID-19 positive individuals for the entire population of North Carolina. On the other hand, the COVID-19 vaccine management system is an online repository of vaccination history.

The researchers found that Pfizer and Moderna vaccines were most effective at preventing a SARS-CoV-2 infection 2 months after the first dose, before gradually declining.

At 2 months after vaccination, the Pfizer and Moderna vaccines were 94.5% and 95.9% effective at preventing a SARS-CoV-2 infection, respectively. The effectiveness of the Pfizer and Moderna vaccines subsequently declined to 66.6% and 80.3% after 7 months, respectively.

The greater effectiveness of the Moderna vaccine (100 microgram [mcg] per dose) could be due to the higher levels of mRNA present in each dose than the Pfizer vaccine (30 mcg per dose).

The single-dose Johnson and Johnson reached peak effectiveness of 74.8% 1 month after vaccination, which gradually reduced to 54.4% after 5 months.

These changes in the effectiveness of the three vaccines did not differ with sex, race, and ethnicity. However, the vaccine effectiveness was lower in individuals over the age of 64 years than in the younger population.

The researchers also compared the patterns of changes in vaccine effectiveness over time in individuals who received their vaccinations at different dates after the vaccines became available in December 2020.

The researchers found that these patterns of change in vaccine effectiveness over time were similar in individuals, regardless of when they received the vaccine. This similarity in patterns of changes in vaccine effectiveness suggests that there was a decline in immunity conferred by the vaccines, regardless of the emergence of the Delta variant.

Furthermore, in individuals who received their first dose of the mRNA vaccines before March 2021, the emergence of the Delta virus was associated with a further 10% and 15% decline in the effectiveness of the Moderna and Pfizer vaccines, respectively.

These data suggest a natural waning of the immunity the vaccines confer and a decline in immunity due to the emergence of the Delta variant.

The researchers then analyzed the effectiveness of the three vaccines in preventing hospitalizations and mortality.

Although more than 800,000 people in North Carolina reported COVID-19 during the study period between December 2020 and September 2021, the researchers only had access to hospitalization and survival data on 40% and 60% of these COVID-19 cases, respectively.

Analyzing these data, the researchers found that all three vaccines, especially the Pfizer and Moderna mRNA vaccines, provided high levels of protection against hospitalization and death at least 6 months after vaccination.

The Pfizer vaccine was 88.7% and 90.5% effective at preventing hospitalization and death, respectively, due to COVID-19 at 7 months after vaccination. Similarly, the Moderna vaccine had an effectiveness of over 94% against hospitalizations (94.1%) and death (95.5%) at the end of 7 months after the first dose.

At 6 months following vaccination, the Johnson & Johnson vaccine was 80% effective in preventing hospitalizations and 70% effective in protecting against death.

Similar to the effectiveness against SARS-CoV-2 infections, the efficacy of all three vaccines in preventing severe illness was lower in individuals aged 65 years and older.

Describing the implications of the study, Dr. Lin said, “First, all three vaccines are durably effective against severe disease leading to hospitalization and death. Thus, unvaccinated people should get vaccinated right away.”

“Second, the Pfizer vaccine is less durable than the Moderna vaccine, so the Pfizer vaccine recipients should get boosters sooner than the Moderna vaccine recipients.”

“Third, older adults have lower vaccine effectiveness and higher risks of hospitalization and death than younger people, so there is a greater urgency for older adults to get booster shots.”

“Fourth, the effectiveness of the Johnson & Johnson vaccine starts to decline after 1 month, so perhaps the Johnson & Johnson vaccine recipients should be administered a second dose after 1 month; if a second dose needs to be taken soon after the first one, there is no practical advantage of taking the Johnson & Johnson vaccine.”

“Finally, because the majority of the vaccinees in the U.S. were vaccinated more than 7 months ago and only a small percentage of the population has received boosters, waning immunity is likely contributing to the breakthrough infections with the Omicron variant. Thus, vaccination and boosting is our best hope against the Omicron variant or any new variants that may arise in the future,” added Dr. Lin.

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