Antibody dependent enhancement and neutralization pattern of sera of SIV infected or HIV2 vaccinated rhesus monkeys.

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Antibody dependent enhancement and neutralization pattern of sera of SIV infected or HIV2 vaccinated rhesus monkeys.

Symp Nonhum Primate Models AIDS. 1990 Nov 28-30;8:45 (abstract no. 29). Unique Identifier : AIDSLINE PRIM8/900029
LeGrand R; Vogt G; Dormont D; SSA/DPTE/DSV/CEA,BP 6, 92265 Fontenay aux Roses, France

Abstract: OBJECTIVE: To evaluate the antibody dependent enhancement (ADE) and the neutralizing titer of sera of rhesus monkeys infected with SIVMAC251 or immunized with Vaccinia-HIV2ROD recombinant viruses and purified HIV2 proteins. METHODS: -Animals: 1) Six Maccaca mulata were infected with 1000 TCID50 of SIVMAC251. 2) Five monkeys were vaccinated with a mixture of 4 different recombinant vaccinia-HIV2 viruses expressing gag, pol, nef and vif genes. 3) Five other animals received the same mixture added with the env gene expressing recombinant. The vaccinated animals were boosted at days 284, 349 and 480 with the purified proteins. Sera samples were periodically drawn. -ADE and Neutralization assay: in a 96 wells microplate, twofold serial dilutions between 1/16 to 1/516 of heat-inactivated sera (56 degrees C, 30mn) were incubated in 50mul containing 10, 1 or 0.1 TCID50 of SIVMAC251 or HIV2ROD for 1h at 37 degrees C (experiments were performed in quadruplicates), and then 50mul of medium containing 3.10(4) HUT78 cells were added to each well. After a second incubation of 1h at 37 degrees C, the plates were washed twice with PBS, and cellular pellets were resuspended in 200 mul of RPMI1640 supplemented with 10% FCS, and cultured in an incubator at 37 degrees C (5% CO2). The identification of syncitia was performed by double microscope examination at days 5 and 7. RESULTS: -1) SIV infected monkeys: all sera exhibited ADE properties. Two monkeys progressively reach a plateau at 1/128 ADE titer, one of them died at day 145 post infection. Three animals showed two peaks of ADE titers, an early one between day 21 and 35, and a second one between day 175 and 205 post infection, one of these monkeys died with an ADE titer of 1/128. Only one animal had detectable neutralizing antibodies (1/128 at day 105), associated with a peak of ADE titer (1/512) at day 49. -2) HIV2 vaccinated monkeys: those which received the mixture containing the recombinant env gene developed neutralizing antibodies against HIV2 ranged between 1/32 and 1/256 (ELISA titers: 10(-5) to 4.10(-5)); two of these monkeys showed ADE titers of 1/512 and 1/128 after the third boost with purified proteins. The animals which received the same mixture lacking env did not neutralize HIV2. All animals lack neutralizing activities against SIVMAC251. CONCLUSION: All SIV infected monkeys showed ADE properties with higher titers than neutralizing ones. Within the HIV2 immunised animals only those vaccinated with the protocole containing the env gene recombinant exhibited detectable neutralizing antibodies. For future vaccine trials, it would be of prime interest to investigate the neutralization and enhancement by antibodies in correlation with the physiopathology of AIDS.

Keywords: Animal Antibodies, Viral/*IMMUNOLOGY HIV-2/GROWTH & DEVELOPMENT/*IMMUNOLOGY Immune Sera Macaca mulatta Neutralization Tests Simian Acquired Immunodeficiency Syndrome/*IMMUNOLOGY SIV/GROWTH & DEVELOPMENT Vaccines, Synthetic Vaccinia Virus/IMMUNOLOGY Viral Envelope Proteins/*IMMUNOLOGY Viral Vaccines Virus Activation ABSTRACT
910730
M9170965

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