Phase 1 clinical trials of the safety and immunogenicity of adjuvanted plasmid DNA vaccines encoding influenza A virus H5 hemagglutinin

• Published in: Vaccine Vol. 28; no. 13; pp. 2565 - 2572
• Main Authors: Smith, Larry R., Wloch, Mary K., Ye, Ming, Reyes, Luane R., Boutsaboualoy, Souphaphone, Dunne, Casey E., Chaplin, Jennifer A., Rusalov, Denis, Rolland, Alain P., Fisher, Cindy L., Al-Ibrahim, Mohamed S., Kabongo, Martin L., Steigbigel, Roy, Belshe, Robert B., Kitt, Ernest R., Chu, Alice H., Moss, Ronald B.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 16.03.2010; Elsevier; Elsevier Limited
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; Adult; Allergy and Immunology; Antibodies; Antibodies, Viral - blood; Antigens; Applied microbiology; Avian flu; Avian influenza virus; Biological and medical sciences; Clinical trials; Deoxyribonucleic acid; DNA; DNA vaccine; Double-Blind Method; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Good Manufacturing Practice; H5N1 influenza virus; Hemagglutination Inhibition Tests; Hemagglutinin Glycoproteins, Influenza Virus - administration & dosage; Hemagglutinin Glycoproteins, Influenza Virus - adverse effects; Hemagglutinin Glycoproteins, Influenza Virus - genetics; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Humans; Immunization, Secondary - methods; Immunogenicity; Influenza A virus - genetics; Influenza A virus - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - genetics; Influenza Vaccines - immunology; Injections, Intramuscular; Male; Microbiology; Miscellaneous; Pandemics; Phosphatidylethanolamines - administration & dosage; Phosphatidylethanolamines - adverse effects; Placebos - administration & dosage; Plasmids; RNA-Binding Proteins - genetics; RNA-Binding Proteins - immunology; Studies; T-Lymphocytes - immunology; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - administration & dosage; Vaccines, DNA - adverse effects; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaxfectin; Viral Core Proteins - genetics; Viral Core Proteins - immunology; Viral Matrix Proteins - genetics; Viral Matrix Proteins - immunology; Virology; Viruses; DNA vaccine; Vaxfectin; H5N1 influenza virus; Hemagglutinin; Orthomyxoviridae; Zoopathogen; Genetic vaccine; Virus; Plasmid; Influenzavirus A; Immunogenicity; Avian influenzavirus; Influenza A virus; Immunological adjuvant; Clinical trial
• ISSN: 0264-410X; 1873-2518; 1873-2518
• DOI: 10.1016/j.vaccine.2010.01.029

Development of vaccines against highly pathogenic avian influenza virus H5N1 subtypes posing a pandemic threat remains a priority. Limitations in manufacturing capacity and production time of conventional inactivated vaccines highlight the need for additional approaches. We conducted two double-blind, placebo-controlled phase 1 studies involving a total of 103 healthy adults who received two intramuscular injections of Vaxfectin ®-adjuvanted plasmid DNA vaccine or placebo 21 days apart. Vaccine cohorts received either a monovalent vaccine containing an A/Vietnam/1203/04 H5 hemagglutinin-encoding plasmid or a trivalent vaccine with plasmids encoding H5, NP, and M2 proteins in doses from 0.1 to 1 mg of DNA/injection. All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of ≥40 and 4-fold rises from baseline were achieved in 47–67% of subjects and H5-specific T-cell responses in 75–100%. Trivalent cohorts had lower HI response rates (≤20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens. Vaxfectin ®-adjuvanted monovalent H5 DNA vaccines were well tolerated and induced HI response rates and titers in the reported range of inactivated protein-based H5 vaccines, suggesting that adjuvanted DNA vaccines with rapid vaccine production could be useful for pandemic control.