Prospects for antibody-based universal influenza vaccines in the context of widespread pre-existing immunity

Abstract

Influenza inflicts significant global mortality and morbidity that can be combated by effective immunization. However, the protective efficacy of current vaccines is limited by both the significant antigenic diversity of the viral hemagglutinin protein and the capacity for rapid antigenic change. This necessitates global influenza surveillance efforts, frequent vaccine reformulation and annual readministration. There is, therefore, tremendous interest in the development of novel strategies to elicit broad and durable protection against both seasonal and pandemic infection. This review presents an overview of candidate universal influenza vaccines designed to elicit cross-protective antibody responses to hemagglutinin. In particular, we focus on the potential impact that widespread pre-existing influenza immunity may play upon the design, testing and deployment of universal influenza vaccines.

Keywords:

• antigenic sin
• influenza
• pandemic
• universal
• vaccine

Acknowledgements

The authors thank Sinthujan Jegaskanda for critical review and comments on the manuscript.

Financial & competing interests disclosure

AK Wheatley is supported by funding from the Australian Research Council. SJ Kent is supported by funding from the National Health and Medical Research Council of Australia. 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.

Key issues

• Antigenic diversity of HA limits the effectiveness of current vaccines.

• Novel universal vaccines are required to elicit broad and lifelong immunity.

• Several vaccine candidates in development look encouraging in animal models of influenza infection.

• However, currently, preclinical development largely fails to account for pre-existing influenza immunity prevalent in human population.

• Baseline influenza immunity may markedly alter vaccine responsiveness and eventual effectiveness.

• More comprehensive animal models are required to fully account for influenza immunity in target populations.