Jacob Atsmon1, Yoseph Caraco2, Sagit Ziv-Sefer3, Dimitry Shaikevich1, Ester Abramov3, Inna Volokhov1, Svetlana Bruzil3, Kirsten Y Haima4, Tanya Gottlieb3, Tamar Ben-Yedidia5. 1. Tel Aviv Sourasky Medical Center CRC,, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Israel. 2. Clinical Pharmacology Unit, Division of Medicine, Hadassah University Hospital, Jerusalem, Israel. 3. BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel. 4. 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. 5. BiondVax Pharmaceuticals Ltd., 14 Einstein Street, Ness Ziona, 74140, Israel. Electronic address: benyedidia@biondvax.com.
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. CLINICALTRIALSGOV REGISTRY NUMBER: NCT01419925.
RCT Entities:
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. CLINICALTRIALSGOV REGISTRY NUMBER: NCT01419925.
Authors: Christopher S Eickhoff; Frances E Terry; Linda Peng; Krystal A Meza; Isaac G Sakala; Daniel Van Aartsen; Leonard Moise; William D Martin; Jill Schriewer; R Mark Buller; Anne S De Groot; Daniel F Hoft Journal: Vaccine Date: 2019-07-19 Impact factor: 3.641