Current COVID boosters offer good protection against severe outcomes but less so against JN.1

The current COVID-19 boosters targeting the Omicron XBB.1.5 subvariant are still offering solid protection against infection, hospitalizations, and death, but are somewhat limited in efficacy against illnesses caused by the JN.1 subvariant, now the dominant strain in the United States, according to a research letter yesterday in the New England Journal of Medicine.

Protection against infection 4 weeks after vaccination was 52%, and against COVID-related hospital illness it was 67%, but during the JN.1-dominant period it dropped to 44% and 60%, respectively.

The authors said the findings underscore the need for new boosters. Next week, the US Food and Drug Administration's VRBPAC (Vaccines and Related Biological Products Advisory Committee) will meet to select COVID and influenza strains to include in updated vaccines.

The elected strain will likely be the JN.1 subvariant.

Need for more targeted vaccines

"The relatively low effectiveness of the XBB.1.5 vaccines against the JN.1 subvariant, together with the waning effectiveness over time, underscores the need for new vaccines targeting the JN.1 strain," said first study author Dan-Yu Lin, PhD, in a press release from the University of North Carolina Gillings School of Public Health.

Lin and colleagues assessed the efficacy of the Moderna, Pfizer, and Novavax boosters from September 11, 2023, to February 21, 2024, in a cohort of approximately 1.8 million people captured in the Nebraska Electronic Disease Surveillance System and the Nebraska State Immunization Information System (NESIIS). 

In total, 218,250 people in the cohort (11.9%) received XBB.1.5 vaccines, of whom 133,403 (61.1%) received the Pfizer–BioNTech vaccine and 84,307 (38.6%) received the Moderna vaccine, the authors said. 

The researchers recorded a total of 21,988 SARS-CoV-2 infections, 1,364 COVID-19–related hospitalizations, and 237 COVID-19–related deaths in the cohort.

Efficacy peaked at 4 weeks

For all three booster vaccines targeting XBB.1.5, efficacy peaked at 1 month, with significant waning at 10 to 20 weeks. 

At 4 weeks after vaccination, the XBB.1.5 vaccines were 52.2% effective at preventing infection (95% confidence interval [CI], 44.6% to 58.7%). Efficacy against infection dropped at 10 weeks to 2.6% (95% CI, 28.1% to 36.8%), and at 20 weeks to 20.4% (95% CI, 6.2% to 32.5%).

The boosters were 66.8% effective at preventing hospitalization at 4 weeks (95% CI, 51.7% to 77.1%), and decreased to 57.1% (95% CI, 40.4% to 69.2%) after 10 weeks.

"The effectiveness against death was higher than that against other end points; however, there remains substantial uncertainty owing to the small number of deaths," the authors said. 

To assess how the booster performed against JN.1, the authors analyzed data comparing people who received the XBB.1.5 vaccines on or before October 25, 2023—when JN.1. was first detected in Nebraska—and those who received them after October 25, 2023.

During that period, boosters provided 44.3% protection against infection at 4 weeks (95% CI, 33.5% to 53.4%) and 60.1% protection against hospitalization (95% CI, 30.9% to 77.0), which likewise waned over time. 

"The vaccine effectiveness was lower in the second cohort than in the first cohort, which indicates that the XBB.1.5 vaccines were less protective against JN.1 than against XBB sublineages," the authors wrote.

It would be worthwhile to deploy new vaccines this fall that target the JN.1. strain.

"It would be worthwhile to deploy new vaccines this fall that target the JN.1. strain," Lin said in the release.