Elsevier

Vaccine

Volume 35, Issue 5, 1 February 2017, Pages 713-715
Vaccine

Short communication
Back to the future: Immunization with M-001 prior to trivalent influenza vaccine in 2011/12 enhanced protective immune responses against 2014/15 epidemic strain

https://doi.org/10.1016/j.vaccine.2016.12.063Get rights and content

Highlights

  • There is an urgent need for a better flu vaccine with broad specificity.

  • M-001 vaccine is based on conserved influenza peptides.

  • M-001 can be used as a primer that enhances HAI response to TIV in human.

  • Sera of elderly immunized with M-001 and TIV contained HAI Ab to future epidemic strain.

  • M-001 influenza vaccine can broaden protective immunity and improve the health of elderly.

Abstract

We previously reported a 2011/12 study in elderly showing that immunization with the universal influenza vaccine candidate, M-001, three weeks before administering trivalent influenza vaccine (TIV) enhanced seroconversion of Hemagglutination Inhibition (HAI) antibodies against known influenza vaccine strains circulating at that time. We now report that those subjects primed with M-001 prior to TIV in 2011 also showed, in their 2011 sera, significantly more HAI antibodies with improved seroprotection and seroconversion against strain A/Switzerland/9715293/2013(H3N2-like) that caused the 2014/15 influenza epidemic and that wasn’t known to circulate in 2011/12. These data indicate that M-001 can provide broadened enhanced immunity extending even to influenza strains destined to circulate in future years. The fact that M-001 stimulates T cell activation and is devoid of HA hypervariable epitopes indicates that such broadened HAI responses effected by M-001 priming is due to extensive T cell priming.

Introduction

Increased morbidity and mortality of elderly individuals from influenza poses major medical public health concerns [1]. Annual epidemics cause both direct and indirect economic loss in the US costing $87B ($56B in elderly) [2]. Current influenza vaccines frequently don’t adequately protect against highly divergent new strains. In 2014/15, influenza vaccine effectiveness was 23% in the general population [3] and in 2012/13 effectiveness was 9% among elderly [4].

Multimeric-001 (M-001), a universal influenza vaccine candidate designed to provide multi-season, multi-strain protection against seasonal and pandemic influenza, is a recombinant protein containing nine linear, conserved and common peptides from influenza virus proteins. M-001 doesn’t contain hemagglutinin hypervariable region epitopes and hence cannot alone elicit HAI antibodies as do licensed inactivated seasonal trivalent influenza vaccines (TIV). Accordingly, before advancing M-001 to large efficacy trials, we are performing safety and immunogenicity trials to identify potential T-cell and humoral immune responses that may serve as immune mechanisms of or markers for protection against influenza.

In 2011/12, we performed a trial in 120 elderly (⩾65) persons (30 per group) [5]: three groups injected with one or two doses of M-001 plus a control group given saline. Three weeks later, all groups were immunized with that season’s TIV. This successful trial demonstrated safety and immunogenicity responses to 2011/12 influenza strains. M-001 alone elicited cell mediated immune responses (CMI) measured by cytokines (IFN-g, gamma interferon) and FACS analysis of T-cell subsets. M-001 priming prior to TIV elicited enhanced HAI seroconversion to 2011/12 vaccine strains as well as to certain former non-vaccine strains. The current report describes HAI antibody responses in the sera of these participants against the influenza strain that caused the 2014/15 epidemic, A/Switzerland/9715293/2013(H3N2-like), a strain not known to circulate at the time of the 2011/12 trial.

Section snippets

Study design

Clinical trial BVX-005 was a two-center, randomized, placebo-controlled study in 120 elderly (⩾65 years old) volunteers conducted with informed consent August 2011 to January 2012 [5]. Participants (30/group) were randomized 1:1:1:1: Three groups received 500 mcg M-001: either non-adjuvanted M-001 twice (Group A); or non-adjuvanted M-001 once (Group B); or M-001 adjuvanted with aluminum phosphate once (Group C); one group received saline and no M-001 (Group D). All received TIV after the last

HAI responses to 2014/15 seasonal epidemic influenza strain A/Switzerland/9715293/2013(H3N2-like) in 2011 sera

The HAI GMT, HAI titer increases, per cent seroprotection and seroconversion in the 2011 sera of each of the four groups are shown (Table 1). Each group of thirty vaccinees primed with M-001 prior to administration of the 2011/12 season TIV showed significant enhanced increases in HAI antibodies against the 2013 A/Switzerland/9715293/2013(H3N2-like) strain as measured by each of these parameters (GMT HAI titers, HAI titer increases, seroprotection and seroconversion) even though that strain did

Discussion

We here show that the M-001 immunization in 2011 three weeks prior to receiving 2011/12 TIV, markedly enhanced immunity against strain A/Switzerland/9715293/2013 that didn’t reportedly circulate during the 2011/12 study. HAI Immune responses to this strain in 2011/12 study participants were examined since this strain caused the 2014/15 US influenza epidemic; indeed, this strain was not included in 2014/15 seasonal TIV [7] since it was not then considered a significant circulating strain. The

Conflict of interest

All authors are employed by BiondVax, the sponsor of the trial described in the manuscript. Dr. Lowell is a director of BiondVax and Dr. Ben-Yedidia is the chief scientist and an inventor of the M-001 universal influenza vaccine; The sponsors of the trial were responsible for its design, analysis, and for preparation of this manuscript.

Acknowledgments

Financial support for the trial was provided by BiondVax Pharmaceuticals Ltd (Israel) and by the Office of Israeli Chief Scientist.

References (11)

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