Improved cell-mediated immune responses in HIV-1-infected asymptomatic individuals after immunization with envelope glycoprotein gp160.
Strong specific T-cell responses to human immunodeficiency virus type 1 (HIV-1) gp160 were induced by immunization with recombinant gp160 (rgp160). It was given as postinfection vaccination to 40 asymptomatic HIV-1 seropositive patients. The participants received 6 doses of 160 micrograms rgp160 administered intramuscularly at 0, 1, 4, 8, 17, and 26 weeks and were monitored for 1 year. Lymphocyte proliferation was performed by cultivating lymphoid cells in vitro with specific antigens and mitogens. After immunization with gp160, specific T-cell proliferative responses were induced in all 40 patients. One week after the sixth immunization at day 180, a substantially increased response was detected in 98% of the patients, with a mean stimulation index value of 195. Furthermore, proliferative responses were also identified, after immunization, against native gp120 and against a peptide representing the V3 region of gp120. In addition to the HIV-specific T-cell responses, increased reactivity to several other non-HIV antigens, including tetanus toxoid, influenza, measles, and cytomegalovirus, were seen after gp160 vaccination. The responses to CMV and measles were interpreted to represent an improved recall antigen response. Such recall antigen responses were few in matched HIV-infected controls immunized with influenza virus only. All patients initially and repeatedly showed a normal capacity of total T-cell activation, evaluated by the mitogen phytohemagglutinin (PHA). The trend in CD4 counts improved in 30 of 40 patients during the year of follow-up. The frequency of increases of proliferative responses to antigens was associated with a better CD4 trend. Addition of zidovudine for 2 weeks after each immunization had no beneficial effects nor did it prevent induction of immune responses. All patients tolerated the immunizations well, and no systemic adverse effects were noted. This is a phase I trial, and no definitive conclusions regarding clinical efficacy can be reached.
Wahren
B
B
Department of Virology, South Hospital, Stockholm, Sweden.
Bratt
G
G
Persson
C
C
Levén
B
B
Hinkula
J
J
Gilljam
G
G
Nordlund
S
S
Eriksson
L
L
Volvovitz
F
F
Broliden
P A
PA
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D015686:Gene Products, env / Q000276:immunology*; D006678:HIV / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D019302:HIV Envelope Protein gp160; D006679:HIV Seropositivity / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D007114:Immunization; D007117:Immunization, Secondary; D007958:Leukocyte Count; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000276:immunology; D011498:Protein Precursors / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D015215:Zidovudine / Q000627:therapeutic use
D015686:Gene Products, env; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; C059762:HIV envelope protein gp120 (305-321); D010446:Peptide Fragments; D011498:Protein Precursors; D011994:Recombinant Proteins; D015215:Zidovudine