Induction of humoral and cellular immunity to simian immunodeficiency virus: what are the requirements for protection?
In an effort to produce a strong humoral and cellular immune response that might protect against simian immunodeficiency virus (SIV) infection, groups of five rhesus macaques each were immunized intramuscularly at 0, 2 and 6 months with 100 micrograms of an inactivated preparation of SIV/Delta B670 in either an oil-in-water emulsion with Ribi Detox, containing mycobacterial cell wall skeleton and monophosphoryl lipid A (CWS/MPL) (group A) or a water-in-oil emulsion with incomplete Freund's adjuvant, containing CWS/MPL for the first two injections (group B). Animals were challenged with 10-100 monkey ID50 of monkey-cell-grown SIVmac251 3 months after the last injection, along with a group of four unvaccinated controls. Group B animals demonstrated the strongest immune responses following immunization, including neutralizing antibody titres against the challenge virus ranging from 160 to 320 and SIV-specific ELISA titres ranging from 10(5)-10(6) on the day of challenge, as well as strong in vitro lymphoproliferative and interleukin-2 (IL-2) production responses to the immunogen. Neutralizing antibody was not detectable in group A animals, ELISA titres were lower (10(2)-10(4)), no in vitro lymphoproliferative responses were observed, and in vitro IL-2 production was less pronounced. No protection against challenge was observed in either group. Moreover, group B animals exhibited a more pronounced clinical response following challenge than either group A animals or controls, consisting of hyperthermia and a greater degree of lymphadenopathy on day 7, followed by hypothermia and generally higher levels of serum viraemia on day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Vaslin
B
B
Laboratoire de Neuropathologie Expérimentale et Neurovirologie, Centre de Recherches du Service de Santé des Armées/Commissariat à l'Energie Atomique, Fontenay aux Roses, France.
Le Grand
R
R
Vogt
G
G
Benveniste
O
O
Gras
G
G
Roques
P
P
Stoeckel
P
P
Salk
P L
PL
Salk
J
J
Dormont
D
D
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D015153:Blotting, Western; D016516:CD4-CD8 Ratio; D002478:Cells, Cultured; D004655:Emulsions; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant; D006801:Humans; D007273:Injections, Intramuscular; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008253:Macaca mulatta; D008297:Male; D011897:Random Allocation; D018449:SAIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000009:adverse effects / Q000276:immunology
D000914:Antibodies, Viral; D004655:Emulsions; D007376:Interleukin-2; D018449:SAIDS Vaccines; D015164:Vaccines, Inactivated; D005620:Freund's Adjuvant