COVID Shots Could Use Another Update, Study Suggests

The updated monovalent XBB.1.5 COVID-19 vaccines were effective against Omicron subvariants circulating during the most recent respiratory virus season, but their effectiveness waned over time, according to a brief report.

The three vaccines updated to target the SARS-CoV-2 XBB.1.5 subvariant — Moderna’s and Pfizer-BioNTech’s mRNA vaccines and the Novavax vaccine — were 66.8% effective against hospitalization at 4 weeks, decreasing to 57.1% after 10 weeks, wrote Dan-Yu Lin, PhD, of the UNC Gillings School of Global Public Health in Chapel Hill, North Carolina, and colleagues.

Vaccine effectiveness against infection was about 52% after 4 weeks, decreasing to 33% after 10 weeks, and to 20% after 20 weeks, the New England Journal of Medicine correspondence showed.

“We expected these vaccines to be effective, especially against hospitalization and death. We also expected the effectiveness to decline over time,” Lin told MedPage Today. “However, we didn’t know beforehand the levels of effectiveness or the duration of protection.”

Although the effectiveness against death was higher — 72% after 4 weeks and 61.4% after 10 weeks — than against infection or hospitalization, “there remains substantial uncertainty,” because there were few deaths in the study population, the authors pointed out.

Data appeared to point to lower effectiveness against infection, hospitalization, and death after the arrival of the JN.1 subvariant, the dominant strain in the U.S. through the end of March of this year.

For those vaccinated before Oct. 26, 2023 — before the JN.1 variant became predominant — the vaccines were 64.4% effective against infection after week 4, decreasing to 40.9% after week 10, and 22.4% after week 18. In comparison, for those vaccinated between Oct. 26, 2023 and Feb. 10, 2024 — when the JN.1 variant was dominant — vaccine effectiveness against infection was 44.3% after week 4 and decreased to 17.4% after week 10.

Effectiveness against hospitalization in those vaccinated during the period before JN.1 was 73.7% after week 8 and 59.1% after week 10, while effectiveness against death was 86.2% at week 4 and 72.9% at week 8 during this period. Among those vaccinated after the JN.1 variant became dominant, effectiveness against hospitalization was 60.1% after week 4 and effectiveness against death was 59.8% after week 4, and both steadily decreased over time.

“It would be worthwhile to develop and deploy new vaccines targeting JN.1 or future strains,” the authors wrote.

The FDA’s Vaccines and Related Biological Products Advisory Committee is set to meet on June 5 to discuss and make recommendations on the selection of the formula for the 2024-2025 season. Signs point to the selection of JN.1 or one of its newer descendants such as KP.2, which currently accounts for an estimated 29% of U.S. cases.

Last month, the World Health Organization (WHO) Technical Advisory Group on COVID-19 Vaccine Composition recommended that future formulations of the COVID-19 vaccine use a monovalent JN.1 lineage as the antigen for future formulations. FDA followed WHO’s recommendations last year in selecting an XBB.1-based strain, approving the monovalent XBB.1.5-directed mRNA vaccines in September 2023.

Further analyses from Lin’s group showed that the XBB.1.5 vaccines were effective across different age groups and among people who had not been previously infected or vaccinated. And Lin commented that the durability of the vaccines “were broadly similar to our previous findings on the durability of bivalent boosters against BQ.1-BQ.1.1 and XBB-XBB.1.5.3.”

For their study, the researchers used data on vaccine uptake from the Nebraska Electronic Disease Surveillance System and the Nebraska State Immunization Information System. Researchers examined all discharge data from hospitals of the Nebraska Hospital Association and reviewed all death certificates in Nebraska to identify deaths related to COVID-19.

In the cohort of 1.8 million people, 218,250 received one of the XBB.1.5 vaccines between Sept. 11, 2023 and Feb. 21, 2024. Among the people who received one of the updated vaccines, 61.1% received the Pfizer-BioNTech vaccine and 38.6% received the Moderna vaccine.

The primary outcomes were COVID-19 infection, hospitalization, hospitalization or death (whichever occurred first), and death. There were 21,988 SARS-CoV-2 reported infections during the study period, with 1,364 COVID-related hospitalizations and 237 COVID-related deaths.

The study did not include results of at-home COVID-19 antigen tests.

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    Katherine Kahn is a staff writer at MedPage Today, covering the infectious diseases beat. She has been a medical writer for over 15 years.

Disclosures

The study was funded by the Dennis Gillings Distinguished Professorship and the National Institutes of Health.

Lin and coauthors reported no relevant financial disclosures.

Primary Source

New England Journal of Medicine

Source Reference: Lin DY, et al “Durability of XBB.1.5 vaccines against omicron subvariants” N Engl J Med 2024; DOI: 10.1056/NEJMc2402779.

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