Immunogenicity of high-dose trivalent inactivated influenza vaccine: a systematic review and meta-analysis

ABSTRACT

Introduction: High-dose trivalent, inactivated, split-virus influenza vaccine (IIV3-HD) has been available in the US since 2009 for adults aged ≥ 65 years. To better understand how IIV3-HD provides improved protection against influenza, we systematically reviewed clinical studies comparing immune responses to IIV3-HD and standard-dose trivalent vaccine (IIV3-SD).

Areas covered: The primary objective was to determine the relative hemagglutination inhibition (HAI) antibody response of IIV3-HD vs. IIV3-SD in adults aged ≥ 65 years. Based on seven randomized studies including more than 18,500 adults aged ≥ 65 years, combined HAI geometric mean titer (GMT) ratios (95% confidence interval) approximately 1 month post-vaccination were 1.74 (1.65–1.83) for influenza A/H1N1, 1.84 (1.73–1.95) for influenza A/H3N2, and 1.47 (1.36–1.58) for influenza B. HAI GMT ratios in these studies were similar irrespective of sex, older age (≥ 75 years), frailty, and underlying conditions. Trends were similar for A/H3N2 neutralization and anti-neuraminidase antibody titers. In immunocompromised individuals, HAI GMT ratios were mostly > 1.

Expert opinion: In agreement with its improved efficacy and effectiveness, IIV3-HD is consistently more immunogenic than IIV3-SD in adults aged ≥ 65 years. IIV3-HD also appears more immunogenic in immunocompromised individuals.

KEYWORDS:

• Elderly adults
• high-dose influenza vaccine
• immunocompromised
• immunogenicity
• systematic review

Article highlights

• A high-dose split-virus inactivated trivalent influenza vaccine (IIV3-HD) containing 60 µg hemagglutinin per strain was approved for adults aged ≥ 65 years in the US in 2009

• Here, we report the results of a systematic review of clinical studies comparing the immunogenicity of IIV3-HD vs. standard-dose inactivated trivalent influenza vaccine (IIV3-SD)

• Meta-analysis of data from seven clinical studies and more than 18,500 individuals showed that, in adults aged ≥ 65 years, hemagglutination inhibition geometric mean titers were 74% higher for influenza A/H1N1, 84% higher for influenza A/H3N2, and 47% higher for influenza B with IIV3-HD than with IIV3-SD

• Higher immunogenicity of IIV3-HD in adults aged ≥ 65 years was found irrespective of sex, older age, underlying high-risk conditions, and frailty

• As expected for a split-virus vaccine, anti-neuraminidase and neutralization antibody responses also indicated higher immunogenicity of IIV3-HD in this population

• The improved immunogenicity of IIV3-HD in this population supports its superior efficacy in randomized clinical trials against laboratory-confirmed influenza and improved real-world vaccine effectiveness against influenza-like illness and associated hospitalization

• Cell-mediated immunity may play a role in the improved protection by IIV3-HD, but further study is needed IIV3-HD is also more immunogenic than IIV3-SD in immunocompromised individuals and in adults aged 50–64 years

Acknowledgments

Medical writing and quality control were provided by 4Clinics (Paris, France) and paid for by Sanofi Pasteur.

Declaration of interest

S Samson, C Salamand, Y Meng, BT Seet, V Landolfi, D Greenberg and R Hollingsworth are employees of Sanofi Pasteur. PS Leventhal is a professional medical writer and employee of 4Clinics France, who’s fees were paid by Sanofi Pasteur. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

S Samson and P Leventhal contributed to the conception, conduct, analysis, and interpretation of the study; preparation of the first draft and editing following drafts for important content; and approval of the final version. C Salamand and Y Meng performed the meta-analysis; contributed to the preparation of the first draft and editing following drafts for important content; and approved of the final version. All other authors participated in conceiving and interpreting the study, editing the manuscript for important content; and approving the final version. All authors agree to be accountable for the content of the article.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This paper was funded by Sanofi Pasteur. Sanofi Pasteur participated in planning the systematic review; analyzing and interpreting the results; and the decision to publish.