Risk of immunodeficiency virus infection may increase with vaccine-induced immune response.
To explore the efficacy of novel complementary prime-boost immunization regimens in a nonhuman primate model for HIV infection, rhesus monkeys primed by different DNA vaccines were boosted with virus-like particles (VLP) and then challenged by repeated low-dose rectal exposure to simian immunodeficiency virus (SIV). Characteristic of the cellular immune response after the VLP booster immunization were high numbers of SIV-specific, gamma interferon-secreting cells after stimulation with inactivated SIV particles, but not SIV peptides, and the absence of detectable levels of CD8(+) T cell responses. Antibodies specific to SIV Gag and SIV Env could be induced in all animals, but, consistent with a poor neutralizing activity at the time of challenge, vaccinated monkeys were not protected from acquisition of infection and did not control viremia. Surprisingly, vaccinees with high numbers of SIV-specific, gamma interferon-secreting cells were infected fastest during the repeated low-dose exposures and the numbers of these immune cells in vaccinated macaques correlated with susceptibility to infection. Thus, in the absence of protective antibodies or cytotoxic T cell responses, vaccine-induced immune responses may increase the susceptibility to acquisition of immunodeficiency virus infection. The results are consistent with the hypothesis that virus-specific T helper cells mediate this detrimental effect and contribute to the inefficacy of past HIV vaccination attempts (e.g., STEP study).
Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
Matthias
M
Tenbusch
Ralf
R
Ignatius
Vladimir
V
Temchura
Ghulam
G
Nabi
Bettina
B
Tippler
Guillaume
G
Stewart-Jones
Andres M
AM
Salazar
Ülrike
Ü
Sauermann
Christiane
C
Stahl-Hennig
Klaus
K
Uberla
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D005260:Female; D015686:Gene Products, env / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007107:Immune System; D007371:Interferon-gamma / Q000378:metabolism; D008251:Macaca; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D010455:Peptides / Q000737:chemistry; D012306:Risk; D018449:SAIDS Vaccines / Q000378:metabolism; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology
D015686:Gene Products, env; D015683:Gene Products, gag; D010455:Peptides; D018449:SAIDS Vaccines; D007371:Interferon-gamma