Preclinical and clinical development of a multi-envelope, DNA-virus-protein (D-V-P) HIV-1 vaccine.
The human immune system has evolved to recognize antigenic diversity, a strength that has been harnessed by vaccine developers to combat numerous pathogens (e.g., pneumococcus, influenza virus, rotavirus). In each case, vaccine cocktails were formulated to include antigenic variants of the target. To combat HIV-1 diversity, we assembled a cocktail vaccine comprising dozens of envelopes, delivered as recombinant DNA, vaccinia virus, and protein for testing in a clinical trial. One vaccinee has now completed vaccinations with no serious adverse events. Preliminary analyses demonstrate early proof-of-principle that a multi-envelope vaccine can elicit neutralizing antibody responses toward heterologous HIV-1 in humans.
Sealy
Robert
R
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Slobod
Karen S
KS
Flynn
Patricia
P
Branum
Kristen
K
Surman
Sherri
S
Jones
Bart
B
Freiden
Pamela
P
Lockey
Timothy
T
Howlett
Nanna
N
Hurwitz
Julia L
JL
D016915:AIDS Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D000818:Animals; D000940:Antigenic Variation / Q000276:immunology; D002986:Clinical Trials as Topic; D004274:DNA, Recombinant / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D019444:Vaccines, DNA / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D004274:DNA, Recombinant; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus; C097729:gp140 envelope protein, Human immunodeficiency virus 1