Vaccine protection against SIVmac infection by high- but not low-dose whole inactivated virus immunogen.
Eight rhesus macaques were immunized intramuscularly four times (0, 1, 2, and 4 months) over a period of 4 months with a formalin-inactivated whole Simian immunodeficiency virus (SIV) vaccine in the presence of muramyl dipeptide (MDP) as adjuvant. Four animals received 0.5 mg and the other four received 0.1 mg immunogen per injection. Three weeks after the final immunization, the vaccinated monkeys along with two control monkeys were challenged intravenously with 50 MID50 of SIVmac251-32H. At the time of challenge, one monkey from the high dose group had a high titer (1:761) of antibody able to neutralize in vitro the homologous 32H strain of SIV mac. All other animals had lower but measurable titers (1:57-1:453), although there was no correlation between the levels of neutralizing antibody and subsequent protection. Upon challenge, three of four animals from the low dose group (plus the nonvaccinated control animals) became infected as demonstrated by reisolation of virus from peripheral blood mononuclear cells, by SIVmac-specific polymerase chain reaction, and by the development of a strong anamnestic response. In the sera from these animals the titer of neutralizing antibody rose to over 1:5,100. All other animals (one from low dose group and all four of the high dose group) remained negative by all parameters at 4 months post challenge. These data indicate that when used in conjunction with MDP, the amount of immunogen required per immunization for protection against challenge is between 0.1 and 0.5 mg.
Hartung
S
S
Paul-Ehrlich-Institut, Langen, Germany.
Norley
S G
SG
Ennen
J
J
Cichutek
K
K
Plesker
R
R
Kurth
R
R
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000920:Antibody-Dependent Cell Cytotoxicity; D001483:Base Sequence; D015153:Blotting, Western; D003601:Cytotoxicity Tests, Immunologic; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D008199:Lymphadenitis / Q000276:immunology; D008253:Macaca mulatta; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000302:isolation & purification; D014765:Viral Vaccines / Q000008:administration & dosage; D014775:Virus Activation / Q000276:immunology*
D000914:Antibodies, Viral; D014765:Viral Vaccines