Long-standing protection of macaques against cell-free HIV-2 with a HIV-2 iscom vaccine.
We investigated the capacity of two immunostimulating-complex (iscom) formulations including inactivated native HIV-2 viral proteins and selected peptides to induce protective immunity against HIV-2 in a nonhuman primate. Four cynomolgus monkeys were first immunized with five i.m. injections of purified detergent-disrupted HIV-2 virions (total dose, 0.7 mg) in iscoms over a period of 16 months. At months 18 and 20, all four macaques were given booster immunizations with iscom-coupled V3-derived synthetic peptides representing a dominating neutralizing region of HIV-2 gp125. Two weeks after the final dose of vaccine, the four vaccinated animals, together with four controls, were challenged i.v. with 10 monkey infectious doses (MID50) of monkey-cell-grown homologous cell-free virus, HIV-2SBL-6669/H5. After the challenge, the four control animals became readily infected; however, three of four vaccinated animals were protected as shown by repeated negative virus isolations and negative polymerase chain reaction for viral DNA and by failure to transmit HIV-2 infection with whole blood and lymph node cells into naive cynomolgus macaques. One of three protected animals showed an anamnestic antibody response to a dominating antigenic site, indicating possible limited virus replication. The vaccine-protected monkeys were subsequently resistant to rechallenge infection at 12, 15, and 18 months after the first challenge, suggesting that a reasonable duration of protective immunity had been induced by the vaccine.
Putkonen
P
P
Department of Immunology, Swedish Institute for Infectious Disease Control, Karolinska Institute, Uppsala.
Björling
E
E
Akerblom
L
L
Thorstensson
R
R
Lövgren
K
K
Benthin
L
L
Chiodi
F
F
Morein
B
B
Biberfeld
G
G
Norrby
E
E
D016915:AIDS Vaccines / Q000008:administration & dosage; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control*; D015498:HIV-2 / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D016882:ISCOMs / Q000008:administration & dosage; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D008198:Lymph Nodes / Q000166:cytology / Q000382:microbiology; D008214:Lymphocytes / Q000382:microbiology; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D016133:Polymerase Chain Reaction
D016915:AIDS Vaccines; D004279:DNA, Viral; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D016882:ISCOMs; D010446:Peptide Fragments