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Enhanced influenza vaccines improve immune responses in older adults

Dr Margaret Shi
24 Dec 2019

Older adults receiving enhanced influenza vaccines have improved humoral and cell-mediated immune responses compared with standard-dose vaccines, a recent local study led by researchers from the University of Hong Kong (HKU) has shown.

 

The use of enhanced influenza vaccines (MF59-adjuvanted trivalent, high-dose [HD] trivalent, or recombinant-haemagglutinin [rHA] quadrivalent vaccine) led to significantly improved immune responses to A(H3N2) compared with standard-dose (SD) quadrivalent vaccine. Of note, more than 4-fold rises in responses to A(H3N2) were achieved in 57 percent of rHA vaccine users, 47 percent of HD vaccine users, and 39 percent MF59-adjuvant vaccine users, compared with only 28 percent of SD vaccine users, according to microneutralization assay. [Clin Infect Dis 2019, doi: 10.1093/cid/ciz1034]

 

On the other hand, immune responses to the B/Victoria component (ie, the selected influenza B vaccine component included in all the four vaccines) were similar across vaccines, with the exception of higher postvaccination antibody titre among those who received the HD vaccines (52 percent).

 

Enhanced influenza vaccines also boosted T-cell responses. A significant increase in IFN-ϒ+ CD8+ T-cell response to B/Victoria from day 7 to day 30 was shown for all three enhanced vaccines, in contrast to a decline in T cells among SD vaccine users. Similarly, all the enhanced vaccines demonstrated significant rises in IFN-ϒ+ CD4+ T-cell responses at 7 and/or 30 days postvaccination, though none of these were significantly higher than the trend for the SD vaccine.

 

In this randomized controlled trial, 200 community-dwelling older adults aged 65–82 years residing Hong Kong were randomly allocated to receive 2017–2018 Northern hemisphere formulations of a SD quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, HD trivalent vaccine, or rHA quadrivalent vaccine. Sera collected from recipients of each vaccine before and at 30 days postvaccination were assessed for antibodies to vaccine strains and to A(H3N2) virus. Influenza-specific CD4+ and CD8+ responses were also assessed in 20 participants per group.

 

Trivalent and quadrivalent vaccines are the mostly commonly used influenza vaccines, with quadrivalent vaccines containing a SD of 15 µg each of A(H1N1), A(H3N2) and B strains, and an additional 15 µg HA of a second B strain. Enhanced influenza vaccines can potentially overcome issues with an ageing immune system and reduced vaccine effectiveness compared with SD vaccines. The trivalent MF59-adjuvanted vaccine includes MF59 in addition to 45 µg of HA and produces a stronger response. The trivalent HD vaccine contains 180 µg of HA, which provides improved protection against influenza among older adults. The quadrivalent rHA-protein vaccine includes 180 µg of HA, and is effective in preventing influenza among adults aged 50 years. [Infect Dis 2019;219:1525-1535; Clin Microbiol Rev 2013;26:476-492; Eur J Epidemiol 2001;17:135-140; Vaccine 2007;25:7656-7663; N Engl J Med 2014;371:635-645; Vaccine 2009;28:379-385; N Engl J Med 2017;376:2427-2436]

 

In the current study, tenderness (range across vaccine groups, 12–20 percent), pain (10–22 percent) and swelling (4–10 percent) were the most frequently reported adverse events following vaccination. Hospitalization was uncommon, and no significant difference in rates of postvaccination hospitalization was observed across the vaccine groups. 

 

“This randomized controlled trial provides a unique comparison of the immune response to multiple enhanced influenza vaccine options for older adults,” said the researchers.

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