Dataset Information

Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis.

ABSTRACT: BACKGROUND:A number of enhanced influenza vaccines have been developed for use in older adults, including high-dose, MF59-adjuvanted, and intradermal vaccines. METHODS:We conducted a systematic review examining the improvements in antibody responses measured by the hemagglutination inhibition assay associated with these enhanced vaccines, compared with each other and with the standard-dose (SD) vaccine using random effects models. RESULTS:Thirty-nine trials were included. Compared with adults aged ?60 years receiving SD vaccines, those receiving enhanced vaccines had significantly higher postvaccination titers (for all vaccine strains) and higher proportions with elevated titers ?40 (for most vaccine strains). High-dose vaccine elicited 82% higher postvaccination titer to A(H3N2) compared with SD vaccine; this was significantly higher than the 52% estimated for MF59-adjuvanted versus SD vaccines (P = .04), which was higher than the 32% estimated for intradermal versus SD vaccines (P < .01). CONCLUSIONS:Overall, by summarizing current evidence, we found that enhanced vaccines had greater antibody responses than the SD vaccine. Indications of differences among enhanced vaccines highlight the fact that further research is needed to compare new vaccine options, especially during seasons with mismatched circulating strains and for immune outcomes other than hemagglutination inhibition titers as well as vaccine efficacy.

SUBMITTER: Ng TWY

PROVIDER: S-EPMC6775043 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis.

Ng Tiffany W Y TWY Cowling Benjamin J BJ Gao Hui Zhi HZ Thompson Mark G MG

The Journal of infectious diseases 20190401 10

<h4>Background</h4>A number of enhanced influenza vaccines have been developed for use in older adults, including high-dose, MF59-adjuvanted, and intradermal vaccines.<h4>Methods</h4>We conducted a systematic review examining the improvements in antibody responses measured by the hemagglutination inhibition assay associated with these enhanced vaccines, compared with each other and with the standard-dose (SD) vaccine using random effects models.<h4>Results</h4>Thirty-nine trials were included. C ...[more]

PMID: 30551178

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Project description:BACKGROUND:Enhanced influenza vaccines may improve protection for older adults, but comparative immunogenicity data are limited. Our objective was to examine immune responses to enhanced influenza vaccines, compared to standard-dose vaccines, in community-dwelling older adults. METHODS:Community-dwelling older adults aged 65-82 years in Hong Kong were randomly allocated (October 2017-January 2018) to receive 2017-2018 Northern hemisphere formulations of a standard-dose quadrivalent vaccine, MF59-adjuvanted trivalent vaccine, high-dose trivalent vaccine, or recombinant-hemagglutinin (rHA) quadrivalent vaccine. Sera collected from 200 recipients of each vaccine before and at 30-days postvaccination were assessed for antibodies to egg-propagated vaccine strains by hemagglutination inhibition (HAI) and to cell-propagated A/Hong Kong/4801/2014(H3N2) virus by microneutralization (MN). Influenza-specific CD4+ and CD8+ T cell responses were assessed in 20 participants per group. RESULTS:Mean fold rises (MFR) in HAI titers to egg-propagated A(H1N1) and A(H3N2) and the MFR in MN to cell-propagated A(H3N2) were statistically significantly higher in the enhanced vaccine groups, compared to the standard-dose vaccine. The MFR in MN to cell-propagated A(H3N2) was highest among rHA recipients (4.7), followed by high-dose (3.4) and MF59-adjuvanted (2.9) recipients, compared to standard-dose recipients (2.3). Similarly, the ratio of postvaccination MN titers among rHA recipients to cell-propagated A(H3N2) recipients was 2.57-fold higher than the standard-dose vaccine, which was statistically higher than the high-dose (1.33-fold) and MF59-adjuvanted (1.43-fold) recipient ratios. Enhanced vaccines also resulted in the boosting of T-cell responses. CONCLUSIONS:In this head-to-head comparison, older adults receiving enhanced vaccines showed improved humoral and cell-mediated immune responses, compared to standard-dose vaccine recipients. CLINICAL TRIALS REGISTRATION:NCT03330132.

Project description:UnlabelledStrategies to optimize responses to seasonal influenza vaccination in older adults include the use of adjuvants, higher antigen doses, and intradermal delivery. In this study adults aged ≥65 years (n = 450) received a single dose of 1 of 2 non-adjuvanted trivalent influenza vaccine (TIV) formulations administered intradermally (ID), both containing 6 µg of A/H1N1 and B, differing in A/H3N2 content (6 µg or 12 µg), or a single dose of 1 of 8 TIV formulations administered intramuscularly (IM) all containing 15 µg of A/H1N1 and B, differing in A/H3N2 hemagglutinin (HA) content (15 µg or 30 µg) and/or in MF59(®) adjuvant content (0%, 25%, 50%, or 100% of the standard dose). This paper focuses on the comparisons of low-dose non-adjuvanted ID, full-dose non-adjuvanted IM and full-dose MF59-adjuvanted IM formulations (n = 270). At day 22 post-vaccination, at least one European licensure immunogenicity criterion was met by all groups against all 3 strains; however, all three criteria were met against all 3 vaccine strains by the low-dose non-adjuvanted ID and the full-dose MF59-adjuvanted IM groups only. The full-dose MF59-adjuvanted IM group elicited significantly higher immune response vs. the low-dose non-adjuvanted ID formulations for most comparisons. The full-dose MF59 adjuvanted IM groups were associated with increased pain at the site of injection (P<0.01) compared to the ID groups, and the low-dose non-adjuvanted ID groups were associated with increased erythema, induration, and swelling at the injection site (P<0.0001) and unsolicited AEs compared with the IM groups. There were no differences between IM and ID groups in the frequencies of subjects experiencing solicited systemic reactions. Overall, while MF59 adjuvantation increased pain at the site of injection, and intradermal delivery increased unsolicited adverse events, erythema, induration, and swelling at the injection site, both strategies of vaccination strongly enhanced the immunogenicity of seasonal influenza vaccine in older adults compared with conventional non-adjuvanted intramuscular delivery.Trial registrationhttp://www.clinicaltrials.gov: NCT00848848.

Project description:ImportanceLow-dose intradermal influenza vaccines could be a suitable alternative to full intramuscular dose during vaccine shortages.ObjectiveTo compare the immunogenicity and safety of the influenza vaccine at reduced or full intradermal doses with full intramuscular doses to inform policy design in the event of vaccine shortages.Data sourcesMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for studies published from 2010 until June 5, 2020.Study selectionAll comparative studies across all ages assessing the immunogenicity or safety of intradermal and intramuscular influenza vaccinations were included.Data extraction and synthesisData were extracted by a single reviewer and verified by a second reviewer. Discrepancies between reviewers were resolved through consensus. Random-effects meta-analysis was conducted.Main outcomes and measuresPrimary outcomes included geometric mean titer, seroconversion, seroprotection, and adverse events.ResultsA total of 30 relevant studies were included; 29 studies were randomized clinical trials with 13 759 total participants, and 1 study was a cohort study of 164 021 participants. There was no statistically significant difference in seroconversion rates between the 3-µg, 6-µg, 7.5-µg, and 9-µg intradermal vaccine doses and the 15-µg intramuscular vaccine dose for each of the H1N1, H3N2, and B strains, but rates were significantly higher with the 15-µg intradermal dose compared with the 15-µg intramuscular dose for the H1N1 strain (rate ratio [RR], 1.10; 95% CI, 1.01-1.20) and B strain (RR, 1.40; 95% CI, 1.13-1.73). Seroprotection rates for the 9-µg and 15-µg intradermal doses did not vary significantly compared with the 15-µg intramuscular dose for all the 3 strains, except for the 15-µg intradermal dose for the H1N1 strain, for which rates were significantly higher (RR, 1.05; 95% CI, 1.01-1.09). Local adverse events were significantly higher with intradermal doses than with the 15-µg intramuscular dose, particularly erythema (3-µg dose: RR, 9.62; 95% CI, 1.07-86.56; 6-µg dose: RR, 23.79; 95% CI, 14.42-39.23; 9-µg dose: RR, 4.56; 95% CI, 3.05-6.82; 15-µg dose: RR, 3.68; 95% CI, 3.19-4.25) and swelling (3-µg dose: RR, 20.16; 95% CI, 4.68-86.82; 9-µg dose: RR, 5.23; 95% CI, 3.58-7.62; 15-µg dose: RR, 3.47 ; 95% CI, 2.21-5.45). Fever and chills were significantly more common with the 9-µg intradermal dose than the 15-µg intramuscular dose (fever: RR, 1.36; 95% CI, 1.03-1.80; chills: RR, 1.24; 95% CI, 1.03-1.50) while all other systemic adverse events were not statistically significant for all other doses.Conclusions and relevanceThese findings suggest that reduced-dose intradermal influenza vaccination could be a reasonable alternative to standard dose intramuscular vaccination.

Dataset Information

Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis.

Publications

Comparative Immunogenicity of Enhanced Seasonal Influenza Vaccines in Older Adults: A Systematic Review and Meta-analysis.

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