Human immunodeficiency virus (HIV-1) gp160-specific lymphocyte proliferative responses of mononuclear leukocytes from HIV-1 recombinant gp160 vaccine recipients

The lymphocyte proliferative responses were studied of 12 volunteers enrolled in a phase I trial of a baculovirus-expressed recombinant human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (rgp160) vaccine. Six subjects received rgp160 and three subjects each received recombinant hepatitis B vaccine or placebo at 0, 1, and 6 months. rgp160 and a control preparation, baculovirus-expressed recombinant HIV-1 p24, were used as in vitro antigens. At day 56, all rgp160 recipients had stimulation indexes (rgp160/rp24) greater than 3.0, and five of six had differences in counts per minute (cpm) greater than 1000. Stimulation indexes were less than 2.0 and cpm differences were less than 150 in all six who did not receive rgp160. Lymphocyte proliferative responses were first noted 2 weeks to 5 months before initial Western blot reactivity and persisted for greater than or equal to 540 days, even among subjects who lost detectable antibody. Thus, the HIV-1 rgp160 vaccine induces persistent cellular immune recognition as demonstrated by lymphocyte proliferation.     

Isotypes and IgG Subclasses of Anti-Fab Antibodies in Human Immunodeficiency Virus-Infected Hemophilia Patients

We reported recently that anti-Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus-infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the IgA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIV+ patients with ARC (p<0.02), HIV+ patients without AIDS/ARC (p<0.0001), HIV-negative (HIV-) patients (p<0.001), or healthy controls (p<0.0001). An inverse association was found between IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, p<10^-6). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. However, IgM-anti-Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA-anti-Fab activity and serum neopterin concentrations (r = 0.310, p<10^-5). IgG-anti-Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity-purified anti-Fab antibodies isolated from sera of AIDS patients bound to rgp120-preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti-Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adsorbance might be a useful approach in the treatment of AIDS.     

Epidermal powder immunization with a recombinant HIV gp120 targets Langerhans cells and induces enhanced immune responses

The recombinant envelope gp120 (rgp120) of human immunodeficiency virus (HIV) is a weak immunogen when administered by intramuscular (IM) injection. In the present study, we report that epidermal powder immunization (EPI) elicits robust antibody responses to the rgp120. EPI of mice with a dose 0.2-5 microg of rgp120 protein elicited geometric mean antibody titers that were 18- to 240-fold higher than that elicited by IM injection using a 5.0 microg dose. Targeting antigen to and mobilization of Langerhans cells (LCs) by EPI may explain the enhanced immunogenicity of the rgp120. EPI with rgp120 using sugar and gold particles as carrier resulted in differential antigen entry into the LCs and differential IgG subclass antibody and cellular immune responses. EPI may serve as a useful tool to evaluate vaccine potential of the rgp120 protein.     

CD4+ lymphocyte function with early human immunodeficiency virus infection.

The pathogenesis of cellular immune deficiency following human immunodeficiency virus (HIV) infection could result from quantitative and/or qualitative dysfunction of the CD4+ lymphocyte population. To better characterize the T-cell response to soluble antigen with HIV infection, we have isolated peripheral blood lymphocytes and purified populations of CD4+ lymphocytes from healthy HIV antibody-positive subjects, patients with acquired immunodeficiency syndrome (AIDS)-related complex (ARC), and healthy HIV antibody-negative controls. T-lymphocyte function was determined by proliferative response to lectin (phytohemagglutinin), phorbol 12-myristate 13-acetate (PMA), calcium ionophore, purified recombinant HIV envelope gp120, tetanus toxoid antigen, and tetanus toxoid antigen in the presence of recombinant gp120 or purified recombinant soluble CD4. PBLs and CD4+ lymphocytes from asymptomatic HIV-infected subjects responded equally well to lectin, PMA, and/or calcium ionophore and to tetanus toxoid as cells from uninfected control subjects. The cells that proliferated in response to a soluble antigenic stimulus did not respond to gp120. Cells from subjects with ARC had a selective antigen recognition defect independent of the number of CD4+ lymphocytes. Recombinant gp120 inhibited CD4+ lymphocyte proliferation to antigenic stimulus by 30-40%. Recombinant soluble CD4, a proposed therapeutic for HIV, had no effect on T-cell response to antigen. A selective antigen recognition response was not compromised early in HIV infection but was compromised in subjects with ARC. Inhibition of proliferation to tetanus toxoid by gp120 suggests that HIV may affect major histocompatibility complex II restricted antigen recognition independent of CD4+ cell loss.     

Functional and immunological characterization of SIV envelope glycoprotein produced in genetically engineered mammalian cells.

Retroviral envelope glycoproteins interact with cell receptors and are targets for antiviral immune responses in infected hosts. Macaque simian immunodeficiency virus (SIVmac) is a T-lymphocytopathic lentivirus which causes an AIDS-like disease in rhesus macaques. The envelope gene of SIVmac encodes a precursor glycoprotein (gp160) which is cleaved into an external domain (gp130) and a transmembrane domain (gp32). To investigate the functional and immunological properties of the SIV external envelope glycoprotein, we have used genetically engineered mammalian cells to produce recombinant gp130 (rgp130). The rgp130 has the appropriate molecular weight, is glycosylated, and has native conformation as determined by binding to the cell receptor for SIV, the CD4 antigen. Rhesus macaques immunized with purified rgp130 formulated in muramyl dipeptide adjuvant generated high titers of antienvelope antibodies. Antibodies from these macaques were tested for in vitro virus neutralization; very low or undetectable levels of neutralization were observed. In contrast, neutralizing antibodies were readily detected in sera from goats immunized with rgp130. With respect to cell-mediated immunity, proliferative responses to rgp130 were demonstrated in peripheral blood monocyte cells (PBMC) from macaques immunized with the recombinant glycoprotein as well as in PBMC from SIV-infected animals. These results show that rgp130 is functional and immunogenic; the potential of rgp130 for protective immunization remains to be determined.     

Effect of dose and immunization schedule on immune response of baboons to recombinant glycoprotein 120 of HIV-1

To evaluate the immunogenicity of purified recombinant envelope glycoprotein of HIV-1 (rgp120) as a potential vaccine for AIDS, the antibody response of 45 baboons to rgp120 was investigated using an adjuvant (alum) and route of administration (intramuscular) suitable for humans. The primary purpose was to evaluate the effects of different doses and immunization schedules on the antibody response to rgp120 in primates. A secondary objective was to evaluate possible adverse consequences of rgp120 immunization. A liquid-phase radioimmunoprecipitation (RIP) assay for detection of rgp120-reactive antibodies revealed that rgp120 doses of 30-300 micrograms per administration resulted in nearly indistinguishable serum antibody responses. However, significant enhancement of serum antibody titers was observed when the interval between the second and third administrations was increased from 4 to 20 w. Although changing the interval significantly altered the magnitude of resulting peak titers, the kinetics of antibody formation were not changed. Thus, of the three schedules of immunization tested, none resulted in a sustained humoral immune response. The significance of the RIP assay for evaluating immune responses was confirmed by analysis showing that the percentage of immunized baboons that developed in vitro HIV-1 serum neutralizing responses was greatest in groups that also exhibited high anti-rgp120 RIP titers. Immunization with rgp120 had no significant adverse effect on any clinical or laboratory parameter monitored over the course of the study.     

A sensitive radioimmunoprecipitation assay for the detection and quantitation of antibodies to the envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1)

A radioimmunoprecipitation (RIP) assay was developed to detect antibodies to the envelope glycoprotein gp120 of the human immunodeficiency virus (HIV-1). The assay, which utilized recombinant gp120 (rgp120), was quantitative, reproducible, and specific for antibodies to rgp120 or antibodies to native gp120 resulting from natural infection with HIV. Polyethylene glycol-8000 (PEG), used in the assay at a final concentration of 10% to precipitate immune complexes, was demonstrated to be effective in titering sera from different animal species. Provided samples were diluted at least 1:100, antibody titers could be determined either by the classical dilution method or by interpolation from a calibration curve prepared with a positive serum. The humoral response of animals immunized with rgp120 was monitored and a positive correlation was found between titers determined in the RIP assay and the ability of the sera to neutralize. In addition, RIP titers of HIV-positive human sera correlated very well with reactivity obtained in a commercial HIV immunoblot assay. The assay has the advantage of quantitation, fast turnaround time, and versatility.     

Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial

BACKGROUND: An objective of the first efficacy trial of a candidate vaccine containing recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein 120 (rgp120) antigens was to assess correlations between antibody responses to rgp120 and the incidence of HIV-1 infection. METHODS: Within the randomized trial (for vaccinees, n=3598; for placebo recipients, n=1805), binding and neutralizing antibody responses to rgp120 were quantitated. A case-cohort design was used to study correlations between antibody levels and HIV-1 incidence. RESULTS: Peak antibody levels were significantly inversely correlated with HIV-1 incidence. The relative risk (RR) of infection was 0.63 (95% confidence interval, 0.45-0.89) per log(10) higher neutralization titer against HIV-1(MN), and the RRs of infection for second-, third-, and fourth-quartile responses of antibody blocking of gp120 binding to soluble CD4 versus first-quartile responses (the lowest responses) were 0.35, 0.28, and 0.22, respectively. CONCLUSIONS: Despite inducing a complex, robust immune response, the vaccine was unable to reduce the incidence of HIV-1. Two interpretations of the correlative results are that the levels of antibodies (i) caused both an increased (low responders) and decreased (high responders) risk of HIV-1 acquisition or (ii) represented a correlate of susceptibility to HIV-1 but had no causal effect on susceptibility. Although the data cannot definitively discriminate between these 2 explanations, (ii) appears to be more likely.     

Characterization of serum neutralization response to the human immunodeficiency virus (HIV)

To determine the clinical significance of human neutralizing antibodies to the human immunodeficiency virus (HIV), we measured serum neutralization in patients with different clinical outcomes following HIV infection. Serum neutralization titers ranged from less than 1:5 to 1:100. The neutralization response after HIV infection appeared slow, with neutralization titers remaining low, at or below 1:5, at 7 months following seroconversion. Comparison of 78 HIV seropositive subjects with AIDS, AIDS-related complex, or no symptoms failed to reveal any significant differences in titer which correlated with clinical status. However, a greater proportion of AIDS patients with Kaposi's sarcoma (11/12) had neutralization titers of 1:20 or greater than did AIDS patients with opportunistic infections (2/11). Serum samples were analyzed by Western blot for their reactivity to specific viral proteins. Clinical status could not be predicted by a particular serological profile. However, sera which reacted with the HIV major envelope glycoprotein gp120 tended to have higher neutralization titers, suggesting that gp120 may be a target of anti-HIV neutralizing antibody in man.     

Cellular and humoral immune responses to a canarypox vaccine containing human immunodeficiency virus type 1 Env, Gag, and Pro in combination with rgp120

Elicitation of both memory cytotoxic T cell responses and human immunodeficiency virus (HIV)-neutralizing antibodies are desirable characteristics of an HIV vaccine regimen. We studied a combination vaccine regimen consisting of a canarypox (CP) vector containing Env, Gag, and Pro, in combination with a recombinant gp120 subunit protein. Twenty-six of 42 subjects who received CP Vac-Env-Pro demonstrated in vitro CD8(+) T cell responses, versus 3 of 17 who received the control CP rabies or gp120 vaccine only (P=.0003); 15 of these 26 demonstrated a CD8(+) cytotoxic T lymphocyte (CTL) response on > or =2 occasions postvaccination. The frequency of CD8(+) CTL response to HIV antigens was similar between vaccinia-naive and vaccinia-immune persons. Rgp120 immunization did not increase the CD8(+) CTL response to HIV type 1 envelope proteins, but rgp120 boosting did markedly enhance the titer and frequency of neutralizing antibodies to the MN strain of HIV. Overall, the combination of a CP Gag, Pro, Env vector, in combination with recombinant gp120, resulted in neutralizing antibodies in 91% of subjects and CD8(+) T cell responses in 62% of subjects. A nonreplicating pox virus shuttle vector vaccine appears to be capable of eliciting CD8(+) CTL responses in most healthy volunteers, whether they were vaccinia naive or vaccinia immune.     

HIV-1 vaccine induced immune responses in newborns of HIV-1 infected mothers

OBJECTIVE: Breast milk transmission continues to account for a large proportion of cases of mother-to-child transmission of HIV-1 worldwide. An effective HIV-1 vaccine coupled with either passive immunization or short-term antiretroviral prophylaxis represents a potential strategy to prevent breast milk transmission. This study evaluated the safety and immunogenicity of ALVAC HIV-1 vaccine with and without a subunit envelope boost in infants born to HIV-1-infected women. DESIGN:: Placebo-controlled, double-blinded study. METHODS: Infants born to HIV-1-infected mothers in the US were immunized with a prime-boost regimen using a canarypox virus HIV-1 vaccine (vCP1452) and a recombinant glycoprotein subunit vaccine (rgp120). Infants (n = 30) were randomized to receive: vCP1452 alone, vCP1452 + rgp120, or corresponding placebos. RESULTS: Local reactions were mild or moderate and no significant systemic toxicities occurred. Subjects receiving both vaccines had gp120-specific binding serum antibodies that were distinguishable from maternal antibody. Repeated gp160-specific lymphoproliferative responses were observed in 75%. Neutralizing activity to HIV-1 homologous to the vaccine strain was observed in 50% of the vCP1452 + rgp120 subjects who had lost maternal antibody by week 24. In some infants HIV-1-specific proliferative and antibody responses persisted until week 104. HIV-1-specific cytotoxic T lymphocyte responses were detected in two subjects in each treatment group; the frequency of HIV-1 specific cytotoxic T lymphocyte responses did not differ between vaccine and placebo recipients. CONCLUSION: The demonstration of vaccine-induced immune responses in early infancy supports further study of HIV-1 vaccination as a strategy to reduce breast milk transmission.     

Zidovudine improves response to pneumococcal vaccine among persons with AIDS and AIDS-related complex

Antibody responses to 23-valent pneumococcal vaccine were studied in 38 individuals infected with human immunodeficiency virus (HIV), including 6 with asymptomatic infection, 24 with AIDS or AIDS-related complex (ARC) receiving treatment with zidovudine, and 8 untreated AIDS/ARC patients. Antibody responses were significantly higher for asymptomatic persons (aggregate geometric mean, 972 ng of antibody nitrogen (AbN)/ml; P less than .001) and AIDS/ARC patients receiving a median of 12 weeks (range, 4-54) of zidovudine therapy (mean, 369 ng of AbN/ml; P less than .001) when compared with untreated AIDS/ARC patients. Antibody responses among zidovudine-treated AIDS/ARC patients were independent of the dose (mean, 629.2 mg/day; range, 100-1200 mg) or duration of zidovudine therapy. For zidovudine-treated AIDS/ARC patients, persistence of an aggregate antibody response 8 months after vaccination was associated with survival at 14 months after vaccination, whereas waning of response was not. Pneumococcal vaccine should be administered as early as possible in the course of HIV infection. Immunization should be delayed for at least 4 weeks for AIDS/ARC patients initiating zidovudine therapy.     

Human immunodeficiency virus type 1 challenge of chimpanzees immunized with recombinant envelope glycoprotein gp120.

The major envelope glycoprotein, gp120, of human immunodeficiency virus type 1 (HIV-1) was purified from a Chinese hamster ovary cell line transfected with a truncated form of the HIV-1 env gene. The recombinant glycoprotein (rgp120) was formulated with aluminum hydroxide adjuvant and was used to immunize chimpanzees. The recombinant preparation was effective in eliciting cellular and humoral immunity as well as immunologic memory. Anti-rgp 120 antibodies reacted with authentic viral gp120 in immunological blot assays and were able to neutralize HIV-1 infectivity in vitro. Sera from the rgp120-immunized animals were able to neutralize HIV-1 pseudotypes of vesicular stomatitis virus prepared from the IIIB isolate, from which the gene encoding rgp120 was derived, as well as two heterologous isolates, ARV-2 and RF. The immune response elicited against the rgp120 was not effective in preventing viral infection after intravenous challenge with HIV-1. The implications of these results on HIV-1 vaccine development are discussed.     

Prognostic significance of quantitative levels of HIV p24 binding capacity in HIV infection

Human immunodeficiency virus, type 1 (HIV-1), produces a chronic infection with a long latency before clinical disease. We followed 214 untreated subjects for 12-42 months to study the natural history of HIV infection: 110 were classified as asymptomatic, 11 as AIDS-related complex (ARC), 15 as AIDS with Kaposi's sarcoma (KS), 31 as AIDS with opportunistic infections (AIDS/OI), and 47 were HIV-seronegative controls. The quantitative capacity of serum to complex HIV p24 antigen, termed the p24 binding capacity (p24 BC), and quantitative levels of HIV p24 antigen in serum were determined at regular intervals. For people in all diagnostic groups, a p24 BC below 31 ng/ml was more closely associated with progression to AIDS/OI than was p24 antigen positivity; 94% of AIDS/OI, 86% of ARC, 56% of AIDS/KS, and 19% of asymptomatic subjects had p24 BC less than 31 ng/ml during the study period, while 67% of AIDS/OI, 27% of ARC, 61% of AIDS/KS, and 20% of asymptomatic subjects were p24 antigenemic. Prospective analysis of 47 asymptomatic seropositive men followed for 3 years, who showed actuarial progression rates to ARC at 4%, 13%, and 23% and to AIDS at 5%, 8%, and 8% at 1, 2, and 3 years, indicated that entry levels of p24 BC below 31 ng/ml were as strongly associated with progression to ARC/AIDS as was p24 antigenemia (p = 0.0003 vs. p = 0.008). The p24 binding capacity assay is a new and convenient methodology to measure immunocomplexing antibody to HIV p24 and is a powerful indicator of progressive HIV disease.     

The safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant gp160 candidate vaccine in humans. NIAID AIDS Vaccine Clinical Trials Network

OBJECTIVE: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate vaccine in humans. SUBJECTS: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups. INTERVENTIONS: The subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540. MEASUREMENTS AND MAIN RESULTS: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time. CONCLUSIONS: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.     

High mannose glycans and sialic acid on gp120 regulate binding of mannose-binding lectin (MBL) to HIV type 1

Mannose-binding lectin (MBL) is a C-type lectin of the innate immune system that binds to carbohydrates on the surface of certain microorganisms. Previous studies showed that MBL binds to gp120, the envelope glycoprotein of HIV-1. gp120 is extensively glycosylated, with N-linked complex and high mannose carbohydrates accounting for about half of the molecular weight. The objectives of this study were to determine the types of glycans on gp120 important for MBL binding and to determine if alteration of complex glycans with neuraminidase (NA) could enhance the interaction of MBL with virus. Lectin blot analyses revealed that MBL interacted with recombinant gp120 (rgp120) from both T cell-tropic and M-tropic virus strains. Treatment of rgp120 with endoglycosidase H (eH) or endoglycosidase F1 (eF1) abrogated binding of MBL, but did not decrease binding of wheat germ agglutinin indicating that high mannose and/or hybrid N-linked glycans were required for MBL binding. Removal of sialic acids from rgp120 with NA enhanced MBL binding. Treatment of intact virus from T cell lines or primary isolates with eF1 also significantly decreased HIV binding to MBL, while treatment with NA substantially increased binding. Treatment of virus with both eF1 and NA did not decrease binding compared to NA alone suggesting that NA treatment exposed binding sites on gp120 that are not high mannose glycans. These studies provide evidence that MBL binds to HIV via high mannose carbohydrates on gp120 and shows that the interaction of MBL with virus is regulated by sialylation.     

Striking inverse association of IgG-anti-Fab gamma antibodies and CD4 cell counts in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex.

The contribution of autoimmune phenomena to the pathogenesis of acquired immunodeficiency syndrome (AIDS) is poorly understood. We investigated the relationship between IgG-anti-Fab gamma autoantibodies and the main immunologic feature of AIDS, the decrease of CD4+ helper lymphocytes. Sera of 33 human immunodeficiency virus (HIV) infected (HIV+) hemophilia patients with AIDS/AIDS-related complex (ARC), 57 HIV+ patients without AIDS/ARC, 23 HIV-negative (HIV-) patients, and 76 healthy controls were tested for antibody activity against the Fab region of IgG. Patients with AIDS/ARC had significantly higher IgG-anti-Fab gamma activity than HIV+ patients without AIDS/ARC, HIV- patients, or controls (P less than .0001). A striking inverse association was found between IgG-anti-Fab gamma and CD4+ cell counts (r = -.69; P less than 10(-6)). Sequential testing in 16 AIDS/ARC patients showed that an increase in the IgG-anti-Fab gamma activity was invariably accompanied by a decrease in the CD4+ cell count. IgG-anti-Fab gamma antibodies may play an important role in the immunopathogenesis of AIDS.     

Humoral immune responses to gag and env proteins from human immunodeficiency virus type 1 in hemophiliac patients

Solid-phase enzyme immunoassays using recombinant gag and env proteins were developed to study humoral immune responses to HIV infection in a cohort of 105 hemophiliac patients. Thirteen patients with ARC or AIDS and 92 asymptomatic patients were studied. A cross-sectional study showed a wide range of antibody responses to gag and env proteins; however, the differences between the ARC/AIDS and asymptomatic patients were statistically significant for both antigens (P less than .0004). In a longitudinal study, antibody levels in sera from 11 asymptomatic patients with gag antibody log units less than or equal to 1.5 were compared to levels in sera from 10 ARC/AIDS patients and 8 asymptomatic patients with gag antibody greater than 1.5. These patient groups were followed for comparable periods of time (67.1-71.7 mo). The asymptomatic patients with low gag antibody and the ARC/AIDS patients showed a similar pattern of antibody response to gag protein overtime. In hemophiliac patients with HIV-1 infection a low titer of antibody to gag protein is not invariably associated with clinical deterioration and is not a useful serologic marker of impending progression to AIDS.     

Antiidiotypic responses to immunization with anti-Leu 3a in human immunodeficiency virus-seropositive individuals.

Anti-idiotypic antibodies to anti-CD4 monoclonal antibodies (MAbs) have been reported to bind to the human immunodeficiency virus (HIV) envelope glycoprotein gp120. To establish whether HIV-infected patients can mount an anti-idiotypic response to murine MAb, four individuals with symptoms of AIDS-related complex (ARC) were immunized over 10 weeks with six intramuscular injections of anti-Leu 3a (1 mg). Despite their immunocompromised state, all patients made anti-constant region and anti-idiotypic antibodies, although the amplitude of the responses varied between individuals. No significant toxic or allergic reactions were seen, and there were no changes in clinical status during the 6 months after immunization. No increase in serum HIV-neutralization titers was seen, and purified anti-idiotypic antibodies did not bind gp120.     

MN and IIIB recombinant glycoprotein 120 vaccine-induced binding antibodies to native envelope glycoprotein of human immunodeficiency virus type 1 primary isolates. National Institute of Allergy and Infectious Disease Aids Vaccine Evaluation Group.

The ability of antibody induced by MN and IIIB recombinant gp120 (rgp120) human immunodeficiency virus type 1 (HIV-1) vaccines to bind to oligomeric native HIV-1 envelope glycoproteins of primary isolates of HIV-1 was measured by flow cytometric indirect immunofluorescence assay (FIFA) in 25 uninfected, healthy adults. After three immunizations, MN rgp120 HIV-1 vaccine given alone and coadministered with IIIB rgp120 HIV-1 vaccine elicited antibody that bound to cells infected with each of a panel of six subtype B strains of HIV-1. Lower levels of vaccine-induced binding antibody were detected against envelope subtype A, D, and (EA) strains of HIV-1 than against subtype B strains. Priming immunization with IIIB rgp120 HIV-1 vaccine alone induced low levels of antibody capable of binding to envelope glycoprotein of primary isolate strains of HIV-1, and booster immunizations with MN rgp120 HIV-1 vaccine resulted in much higher antibody levels. We conclude that MN rgp120 HIV-1 vaccine was an effective inducer of antibody to native envelope glycoproteins of antigenically diverse primary isolates of HIV-1.