Safety and immunogenicity of multimeric-001--a novel universal influenza vaccine.
OBJECTIVE
A new vaccine, Multimeric-001, containing conserved linear epitopes from the HA, NP, and M1 proteins of influenza type A and type B strains was designed to protect against seasonal and pandemic influenza virus strains, regardless of mutations. We assessed its safety and tolerability and characterized humoral and cellular immune responses elicited by its administration.


METHODS
Sixty healthy volunteers received either 250 or 500 μg injections, with or without adjuvant (Montanide ISA 51VG), or matching placebo. Two intramuscular injections were administered, 21 days apart.


RESULTS
Treatment was well tolerated and no significant adverse events were noted. Forty-two days after first injection, there was a 50-fold and 37-fold increase in IgG titers against Multimeric-001 protein, following the adjuvanted 500 and 250 μg doses, respectively. Sera from immunized subjects lysed MDCK cells infected with strains of influenza representing the major strains that infect humans: H1N1, H3N2, and influenza B. Proliferation of peripheral blood mononuclear cells as well as increase in IL-2 and IFN-gamma secretion occurred following incubation with the vaccine.


CONCLUSIONS
This vaccine model differs fundamentally from the current influenza virus vaccines, as it does not contain the variable regions of the virus hemagglutinin and hence does not induce hemagglutination inhibition antibodies that serve as surrogate markers for protection. In order to demonstrate the potential efficacy of the Multimeric-001, an alternative assay was employed, in which the lysis of MDCK cells infected with different virus strains was shown, with the involvement of the complement mechanism. The humoral and cellular responses suggest a cross-immunity of the vaccine toward influenza virus strains regardless of mutations. These results corroborate the protective effect of the vaccine, previously shown in animals. Larger-scale studies are under way to further substantiate the safety and efficacy of the vaccine candidate.
Clinical Research Center, Tel Aviv Sourasky Medical Center, affiliated to Sackler Faculty of Medicine, Tel Aviv University, 6 Weizmann Street, Tel Aviv, 64239, Israel. katsmon@bezeqint.net
Jacob
J
Atsmon
Efrat
E
Kate-Ilovitz
Dimitry
D
Shaikevich
Yossi
Y
Singer
Inna
I
Volokhov
Kirsten Y
KY
Haim
Tamar
T
Ben-Yedidia
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000293:Adolescent; D000328:Adult; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D002460:Cell Line; D004285:Dogs; D000939:Epitopes / Q000008:administration & dosage*; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008875:Middle Aged; D009698:Nucleoproteins / Q000276:immunology; D009829:Oleic Acids / Q000008:administration & dosage*; D014763:Viral Matrix Proteins / Q000276:immunology; D055815:Young Adult
D000276:Adjuvants, Immunologic; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007376:Interleukin-2; D009698:Nucleoproteins; D009829:Oleic Acids; D014763:Viral Matrix Proteins; C477385:montanide ISA 51; D008353:Mannitol; D007371:Interferon-gamma