Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative.
OBJECTIVE
To evaluate the safety and immunogenicity of a polyvalent (PV) HIV envelope synthetic peptide immunogen, C4-V3. The immunogen comprised four peptides containing T-helper epitopes from the fourth constant region (C4) of gp120 of HIV-1MN, and T-helper, cytotoxic T-lymphocyte HLA-B7-restricted, and B-cell neutralizing epitopes from the gp120 third variable region (V3) of four clade B HIV-1 isolates, HIV-1MN, HIV-1RF, HIV-1EV91, and HIV-1Can0A.


METHODS
A pilot, Phase I controlled trial [Division of AIDS Treatment Research Initiative (DATRI) 010] conducted at a single center.


METHODS
Ten HIV-infected, HLA-B7-positive patients with CD4 cells > 500 x 10(6)/l were enrolled. Eight patients received the C4-V3 PV immunogen emulsified in incomplete Freund's adjuvant in five intramuscular injections over 24 weeks, and two controls received incomplete Freund's adjuvant alone. All subjects were followed for 52 weeks.


RESULTS
Four out of eight C4-V3 PV recipients generated at least fourfold rise in serum antibody titers to at least three immunogen peptides in contrast to none of the control subjects. Four out of eight C4-V3 PV recipients and none of the controls had an at least fourfold rise in neutralizing antibodies to either HIV-1MN, HIV-1RF, or HIV-1(4489-5) laboratory-adapted HIV isolates. 3H-Thymidine incorporation assays of peripheral blood mononuclear cells increased at least fivefold over the baseline stimulation index to at least one of the immunogen peptides in two consecutive post-immunization timepoints in five out of eight C4-V3 PV recipients versus none of the controls. CD4 cell counts and plasma HIV RNA levels did not change in patients who received either C4-V3 PV or adjuvant alone. Adverse events consisted primarily of grade 1 injection site reactions in six subjects (four C4-V3 recipients, two controls).


CONCLUSIONS
C4-V3 PV synthetic peptides demonstrated both immunogenicity and safety in HIV-infected patients.
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
J A
JA
Bartlett
S S
SS
Wasserman
C B
CB
Hicks
R T
RT
Dodge
K J
KJ
Weinhold
C O
CO
Tacket
N
N
Ketter
A E
AE
Wittek
T J
TJ
Palker
B F
BF
Haynes
D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000328:Adult; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000032:analysis; D002461:Cell Line, Transformed; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000009:adverse effects / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D015793:HLA-B7 Antigen / Q000276:immunology*; D006801:Humans; D007428:Intradermal Tests; D016131:Lymphocyte Subsets / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010865:Pilot Projects; D012367:RNA, Viral / Q000097:blood; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*
D016915:AIDS Vaccines; D015703:Antigens, CD; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015793:HLA-B7 Antigen; D012367:RNA, Viral; D014614:Vaccines, Synthetic