title: Priming by a novel universal influenza vaccine (Multimeric-001)-a gateway for improving immune response in the elderly population.
abstract: BACKGROUND
  A new vaccine, "Multimeric-001" (M-001) has been recently developed, containing conserved, common linear influenza epitopes that activate both cellular and humoral arms of the immune system against a wide variety of influenza A and B strains. Apart from its direct action, M-001 is an attractive candidate for priming immune responses to seasonal influenza vaccine for the elderly population. The current clinical study was designed to assess M-001's standalone and priming action in participants over 65 years old. Evaluation of standalone action is based on induction of cell mediated immunity (CMI), since M-001 alone does not induce hemagglutinin inhibition (HAI) antibodies.
  
  
  METHODS
  This was a two-center, randomized, placebo-controlled study. 120 participants were randomized 1:1:1:1 into four groups to receive either two sequential non-adjuvanted or a single non-adjuvanted or a single adjuvanted intramuscular injection of 500 mcg M-001 (treatment), or one placebo (saline) injection, before receiving the trivalent inactivated influenza vaccine (TIV). Due to visual differences between placebo and treatment the study was partially blinded. HAI was evaluated at baseline and 3 weeks after standard TIV vaccination as a measure of M-001's efficacy. CMI responses were evaluated in a subset (10/group) of the participants. Participants were monitored for safety throughout the study.
  
  
  RESULTS
  Overall the treatment was well-tolerated and safe, though sample sizes allowed only limited statistical analysis. M-001 priming resulted in enhanced seroconversion towards all three TIV strains, compared to priming with placebo. Significant elevation of influenza-specific CMI was observed following immunization with M-001 alone.
  
  
  CONCLUSIONS
  The standalone and priming actions of M-001 were demonstrated in elderly participants despite the limitations of small population size and pre-existing HAI antibody titers in some participants. As a standalone vaccine, M-001 induced significant CMI to multiple strains and as a primer, M-001 enhanced HAI responses. Larger scale studies are warranted.
  NCT01419925.
authors.affiliation: Tel Aviv Sourasky Medical Center CRC,, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel.
authors.forename: Jacob
authors.initials: J
authors.lastname: Atsmon
authors.affiliation: Clinical Pharmacology Unit, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Yoseph
authors.initials: Y
authors.lastname: Caraco
authors.affiliation: BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel.
authors.forename: Sagit
authors.initials: S
authors.lastname: Ziv-Sefer
authors.affiliation: Tel Aviv Sourasky Medical Center CRC,, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel.
authors.forename: Dimitry
authors.initials: D
authors.lastname: Shaikevich
authors.affiliation: BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel.
authors.forename: Ester
authors.initials: E
authors.lastname: Abramov
authors.affiliation: Tel Aviv Sourasky Medical Center CRC,, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel.
authors.forename: Inna
authors.initials: I
authors.lastname: Volokhov
authors.affiliation: BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Bruzil
authors.affiliation: Tel Aviv Sourasky Medical Center CRC,, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel; Clinical Pharmacology Unit, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel; BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel.
authors.forename: Kirsten Y
authors.initials: KY
authors.lastname: Haima
authors.affiliation: BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel.
authors.forename: Tanya
authors.initials: T
authors.lastname: Gottlieb
authors.affiliation: BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel. Electronic address: benyedidia@biondvax.com.
authors.forename: Tamar
authors.initials: T
authors.lastname: Ben-Yedidia
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007252:Influenza Vaccines / Q000627:therapeutic use*; D007251:Influenza, Human / Q000517:prevention & control*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000627:therapeutic use
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic
keywords: CMI; Elderly; HAI; Influenza; Multimeric-001; Prime boost; Universal