Effective Influenza Vaccine for Elderly Remains Elusive

A meta-analysis of studies examining seasonal immunization effectiveness in preventing hospitalization for severe influenza has found that less protection is achieved in the elderly, particularly against influenza A(H3N2) viruses.

Marc Rondy, PhD (pictured) — an epidemiologist at Epiconcept, Paris, France — and colleagues conducted the analysis of 30 test-negative design (TND) case-control studies conducted between the 2010-11 and 2014-15 seasons.

“Influenza vaccines provided moderate protection against influenza-associated hospitalizations among adults," researchers wrote. "They seemed to provide low protection among elderly in seasons where vaccine and circulating A(H3N2) strains were antigenically variant.”

One study conducted after those examined by Rondy and colleagues, published in Journal of Infectious Diseases one month before their meta-analysis in another journal, adds that a frail condition besides chronological age is a significant factor in the increased vulnerability.

In commentary accompanying that study, Kathleen Neuzil, MD, MPH and Wilbur Chen, MD, MS, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, emphasized the relevance of the decades-long recommendation for universal vaccination of persons aged 65 years and older, and consequences of routinely having lower levels of participation.

"Vaccination coverage of this degree is unacceptable for our childhood immunization programs, yet has become the accepted norm for adults," Neuzil and Chen wrote.

In the older adult population, the researchers observed, influenza has become a significantly important burden of health.

“Hospitalizations are consistently highest among persons aged ≥65years of age,” Neuzil and Chen wrote. “Similarly, deaths are much more frequent among older persons than younger persons."

Rondy and colleagues focused their meta-analysis on studies of influenza vaccine effectiveness (IVE) in preventing these most severe outcomes, examining IVE against laboratory-confirmed influenza-associated hospitalizations, stratified by the age groups of 18-64 years, and 65 years or older, as well as by influenza subtype/lineage and influenza season.

They limited their examination to studies applying TND to minimize heterogeneity of their analysis. and in recognizing this design as a preferred method for evaluating influenza vaccine effectiveness. The approach examines patients meeting the same clinical criteria and estimates vaccine effectiveness from the relative difference between the odds of vaccination among patients testing positive and those testing negative for influenza viruses.

The moderate protection afforded by vaccination against influenza-associated hospitalization was reflected in the pooled IVE estimate of 51% for adults younger than 65 years of age, and 37% in those 65 years or older. Seasonal vaccine effectiveness against influenza A(H1N1)pdm09 viruses was 48% overall, with 50% and 33% in younger and older adults, respectively.

With circulating A(H3N2) virus antigenically similar to the vaccine, IVE was 59% in younger adults and 43% in those older than 65 years of age. There was substantial disparity in IVE, however, when circulating A(H3N2) was dissimilar to the vaccine: 46% in younger adults compared to 14% in older adults.

"Lower IVE point estimates during seasons predominated by variant A(H3N2) viruses were noted for all adults, but the difference was only statistically significant among persons 65 years and older," researchers wrote. "The reasons why a poorly matched A(H3N3) vaccine component would provide less protection to older adults is unclear, but may include a narrower and more specific immune response to influenza vaccines and possibly age-cohort specific differences in A(H3N3) virus exposure history."

The review, "Effectiveness of influenza vaccines in preventing severe influenza illness among adults: A systematic review and meta-analysis of test-negative design case-control studies," was published online in Journal of Infection last month.