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


METHODS
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 1mg of DNA/injection.


RESULTS
All doses were well tolerated without vaccine-related serious adverse events or discontinuations. In the monovalent cohorts, hemagglutination inhibition (HI) titers of > or =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 (< or = 20%), but 72% of subjects achieved T-cell and/or antibody responses to one or more antigens.


CONCLUSIONS
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.
Smith
Larry R
LR
Vical Incorporated, 10390 Pacific Center Court, San Diego, CA 92121, United States. lsmith@vical.com
Wloch
Mary K
MK
Ye
Ming
M
Reyes
Luane R
LR
Boutsaboualoy
Souphaphone
S
Dunne
Casey E
CE
Chaplin
Jennifer A
JA
Rusalov
Denis
D
Rolland
Alain P
AP
Fisher
Cindy L
CL
Al-Ibrahim
Mohamed S
MS
Kabongo
Martin L
ML
Steigbigel
Roy
R
Belshe
Robert B
RB
Kitt
Ernest R
ER
Chu
Alice H
AH
Moss
Ronald B
RB
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005260:Female; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D008297:Male; D019590:Nucleocapsid Proteins; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage; D010957:Plasmids; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology; D000086082:Viroporin Proteins
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D019590:Nucleocapsid Proteins; D010714:Phosphatidylethanolamines; D010919:Placebos; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins; C048842:NP protein, Influenza A virus; C109963:hemagglutinin, avian influenza A virus; C460866:vaxfectin