Enhanced Influenza Vaccines Offer Improved Antibody Response in Older Adults

child getting flu vaccine
Compared with a standard-dose influenza vaccine, several enhanced influenza vaccines improved humoral and cell-mediated immune responses in older adults.

Compared with a standard-dose influenza vaccine, several enhanced influenza vaccines improved humoral and cell-mediated immune responses in older adults, according to study results published in Clinical Infectious Diseases.

In this randomized controlled trial (ClinicalTrials.gov Identifier: NCT03330132), 1861 community-dwelling older adults aged 65 to 82 years in Hong Kong were assigned to 1 of 4 influenza vaccine groups: a standard-dose quadrivalent vaccine (n=508; 0.5 mL FluQuadri™, Sanofi Pasteur), a trivalent MF59-adjuvanted vaccine (n=508; 0.5 mL FLUAD®, Seqirus), a trivalent high-dose vaccine (n=510; 0.5 mL Fluzone® High-Dose, Sanofi Pasteur), and a quadrivalent recombinant-hemagglutinin vaccine (n=335; 0.5 mL Flublok®, Sanofi Pasteur). All vaccines included the strains recommended for the Northern hemisphere 2017-2018 formulation.

In 200 random participants from each vaccine group, investigators assessed sera using hemagglutination inhibition assays against egg-propagated vaccine strains A/Singapore/GP1908/2015 (A/Michigan/45/2015[H1N1]-like virus), A/Hong Kong/4801/2014(H3N2), B Brisbane/60/2008, and B/Phuket/3073/2013, and by virus microneutralization against cell-propagated A/Hong Kong/4801/2014(H3N2). Sera samples were evaluated before and 30 days postvaccination. In addition, influenza-specific CD4+ and CD8+ T-cell responses against influenza A (H1N1), A(H3N2), and B vaccine strains were assessed in 20 participants from each group.

Mean fold rise from day 0 to day 30 for A(H1N1) were significantly higher for all 3 enhanced vaccines (range, 5.3-6.1) compared with the standard-dose vaccine (4.1). Of note, the percentage of participants who achieved very high titers of ≥160 were significantly higher for all 3 enhanced vaccines (45%-55%), compared with the standard-dose vaccine (35%).

Compared with the standard-dose vaccine, participants of all 3 enhanced vaccines achieved higher postvaccination geometric mean titers and greater mean fold rises to both the egg-propagated A(H3N2) by hemagglutination inhibition assay and the cell-propagated A(H3N2) by microneutralization assay. Among recipients of the standard-dose, 28% achieved ≥4-fold rises in microneutralization assay responses to cell-propagated A(H3N2) compared with 39% of trivalent MF59-adjuvanted recipients, 47% of trivalent high-dose recipients, and 57% of quadrivalent recombinant-hemagglutinin recipients (P <.01).

The ratio of postvaccination microneutralization titers among quadrivalent recombinant-hemagglutinin vaccine recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the trivalent high-dose vaccine (1.33-fold) and trivalent MF59-adjuvanted vaccine (1.43-fold) ratios.

The findings for influenza B viruses were less clear, because the antibody responses to the influenza B/Victoria-lineage component were high for all vaccines.

Related Articles

Enhanced vaccines also resulted in the boosting of T-cell responses.

Because vaccine immunogenicity is not equivalent to vaccine efficacy, future efficacy trials and/or well-controlled effectiveness studies are needed. “[T]he findings from this ongoing immunogenicity trial can help to establish the conditions for…more definitive evaluations, including what differences in efficacy/effectiveness might plausibly be expected,” concluded the researchers.

Disclosure: Benjamin J. Cowling has received honoraria from Sanofi and Roche for advisory committees.


Cowling BJ, Perera RAPM, Valkenburg SA, et al. Comparative immunogenicity of several enhanced influenza vaccine options for older adults: a randomized, controlled trial [published online December 12, 2019]. Clin Infect Dis. doi:10.1093/cid/ciz1034