HLA-DR gene frequencies in a Zaïrean population with particular reference to rheumatic diseases.

Epidemiological studies have shown that rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus are uncommon in black Africans, and in this population the prevalence and the clinical features of these rheumatic diseases are variable. Environmental and genetic factors have been pointed out to explain this variability. In the present study, HLA-DR genes have been determined in a Zaïrean population in order to compare our results with those found elsewhere in other black populations of the same Bantu origin. Our results show that the frequency of HLA-DR1 is higher than in Nigerians, Zimbabweans and Xhosas, the decrease in Xhosas being statistically significant (p < 0.006). The HLA-DR3 frequency is higher in Zaïreans than in Nigerians but not significantly, while it is lower than in Xhosas (p < 0.003) and in Zimbabweans (not significant). The HLA-DR4 frequency is higher in Zaïreans than in Nigerians but it is lower than in Xhosas and Zimbabweans; the differences are not statistically significant. The HLA-DR8 frequency is lower in Zaïreans than in Nigerians while it is higher than in Xhosas (p < 0.002) and in Zimbabweans (not significant). These data suggest that genetic factors partly explain the clinical and epidemiological variability of rheumatic diseases in black Africans.

Therapeutic effect of an anti-HIV candidate vaccine.

A chimpanzee infected with the HIV since 8 months and presenting regularly with antigenemia was inoculated with a candidate vaccine. It received 3 doses, one dose every 15 days. Thirty days after the third injection, we noted the disappearance of the HIV antigens in the serum and its persistence in the lysate of the cells. We noted also a strong precipitation reaction both in the tube and in the gel between the antibodies and the antigens released by the lysis of the cells. The analysis of this precipitate demonstrated that it was constituted of immune complexes in which the antibodies were of high affinity. At the 240th day after the third injection of the candidate vaccine we noted the disappearance of the HIV antigens in the lysate of cells as well. From these results, we conclude that the candidate vaccine we tested can elicit high affinity antibodies able to clear the HIV antigens and destroy the cells containing the HIV antigens probably with the help of specific killer cells.

Removal of gp160 induced bio-hazards for a safe AIDS vaccine candidate.

In the first AIDS vaccine trial, immunizing preparations were based on HIV-1 Env protein (gp160). Immunogenic properties of gp160 which trigger both a humoral and cellular immune response have since justified its use in various vaccine programs, both past and present. Many reports however have underlined deleterious effects on the immune system--anti-HIV-1 enhanced antibodies, anti-CD4 autoantibodies, and inhibition of T cell activation by HIV-1--particularly associated with the Env protein. The present study shows that gp160 presented in a biologically inactivated but immunogenic form, as used in our trial, could avoid these complications. Bio-hazards associated with gp160 which indeed could be removed by appropriate treatment of the native protein, should be taken into consideration in AIDS vaccine programs.

[Immunization against the human immunodeficiency virus in Zaire]. / Immunisation contre le virus de l'immunodéficience humaine au Zaïre.

The first experimental immunization of human against the AIDS retrovirus HIV-1 was started in a series of HIV seronegative healthy volunteers in november 1986. Priming used a vaccinia virus recombinant (V25) expressing Gp 160 env determinants of HTLV III B at the surface of infected cells. This priming which induced a weak immune reaction was performed on HIV seronegative French and Zaïrian individuals living in Zaïre (Kinshasa). These results prompted to boost the primary immune response. Four different protocols were used: slow drip intravenous infusion with paraformaldehyde fixed autologous cells infected with V25 (first protocol), repeated scarification with V25 for the second protocol. The third protocol used scarifications with fragment of Gp 120 env protein, and the fourth protocol used intramuscular injections of purified autologous cell membrane infected with V25. Results of the immune reaction obtained after these boosts: The three last protocols showed a cell mediated immunity (CMI) that not significantly enhanced in comparison with CMI obtained after V25 priming alone. Moreover, the sera showed low and variable neutralizing antibodies titers one to four months after boosting. By contrast boosting with V25 infected fixed cells (D.Z. individual) provide strong humoral and cellular group specific anamnestic immune response. Indeed, high levels of antibodies to viral envelope and neutralizing antibodies against divergent HIV-1 strains were observed. Group specific CMI and cell mediated cytotoxicity were enhanced by boosts. Skin-tests showed high mediated and delayed hypersensitivity to GP 160 in vivo. For the first time, these results show that an immune stage against HIV can be obtained in a man.

PIP: The 1st experimental immunization of humans against the AIDS retrovirus HIV-1 was begun in November 1986 among a group of HIV-seronegative healthy volunteers. A priming, involving a vaccine virus recombinant (V25) expressing Gp 160 env determinants of HTLV-III B at the surface of the infected cells was utilized. This priming, which induced a weak immune reaction, was performed on HIV-seronegative French and Zairian individuals living in Kinshasa, Zaire. These results prompted a boost to the primary immune response. 4 different protocols were used: the slow drip intravenous infusion with paraformaldehyde-fixed autologous cells infected with V25; repeated scarification with V25 for the 2nd protocol; scarifications with fragments of Gp 120 env protein; and intramuscular injections of purified autologous cell membrane infected with V25. The results of the immune reaction obtained after these boosts indicated the following: The last 3 protocols showed a cell- mediated immunity (CMI) that did not significantly enhance in comparison with CMI obtained after V25 priming alone. Moreover, the sera showed low and variable neutralizing antibody titers 1-4 months after boosting. By contrast, boosting with V25 infected fixed cells (D.Z.) provided strong humoral and cellular group specific anamnestic immune responses. Indeed, high levels of antibodies to viral envelope and neutralizing antibodies against divergent HIV-1 strains were observed. Group- specific CMI and cell mediated cytotoxicity were enhanced by boosts. Skin tests showed high mediated and delayed hypersensitivity to Gp 160 in vivo. For the 1st time, these results show that an immune state against HIV can be obtained in a man. (author's modified)

Antigenic peptides recognized by T lymphocytes from AIDS viral envelope-immune humans.

T-lymphocyte immunity is likely to be an important component of the immune defence against the AIDS virus, because helper T cells are necessary for the antibody response as well as the cytotoxic response. We have previously predicted two antigenic sites of the viral envelope protein gp120 likely to be recognized by T lymphocytes, based on their ability to fold as amphipathic helices, and have demonstrated that these are recognized by T cells of mice immunized with gp120 (ref. 1). A peptide corresponding to one of these sites can also be induce immunity in mice to the whole gp120 protein. Because many clinically healthy seropositive blood donors have already lost their T-cell proliferative response to specific antigen, we tested the response to these synthetic peptides of lymphocytes from 14 healthy human volunteers who had been immunized with a recombinant vaccinia virus containing the AIDS viral envelope gene and boosted with a recombinant fragment. Eight of the 14 responded to one peptide, and four to the other peptide, not included in the boost. These antigenic sites recognized by human T cells may be useful components of a vaccine against AIDS. We also found a correlation between boosting with antigen-antibody complexes (compared to free antigen) and higher stimulation indices, suggesting a more effective method of immunization.

A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS.

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.

[Pericarditis and acquired immunodeficiency syndrome]. / Péricardite et syndrome d'immunodéficience acquise.

In order to evaluate the frequency and clinical features of pericarditis caused by the HIV virus, 17 patients (mean age 28 years) presenting with pericarditis were investigated at the University Clinics of Mont-Amba (Zaïre), between January, 1985 and December, 1986. The clinical diagnosis of AIDS had been made on the basis of the WHO criteria. An ELISA test, a tuberculin test and a T4-lymphocyte count were performed in all patients. Cardiovascular explorations were limited to electrocardiography, radiography of the chest, echocardiography and pericardial needle aspiration. HIV pericarditis accounted for 50 p. 100 of all cases of pericarditis. It was either dry or effusive with little fluid, and its clinical signs at the early stage of AIDS were retrosternal pain and pericardial friction rub. A search for anti-HIV antibodies may be negative at that stage. Diagnostic errors can be avoided if the tuberculin test is negative and if an ELISA test is performed repeatedly at 3 weeks' intervals. Pericarditis should be counted among the minor signs of AIDS.

PIP: Cardiac manifestations have not attracted the attention of AIDS researchers as much as pulmonary, digestive tract, and nervous system effects. Recent autopsies on AIDS patients, however, have revealed cardiac lesions of several types, including pericarditis. To evaluate the frequency and clinical aspects of pericarditis due to HIV infection, 17 subjects with AIDS-associated pericarditis were studied at the University Clinics in Mont-Amba, Kinshasa, Zaire, between January 1985-December 1986. Subjects ranged in age from 20-50 years and averaged 28 years. 11 women were prostitutes and 6 men reported having at least 5 sexual partners. The clinical diagnosis of AIDS was based on World Health Organization criteria. An ELISA test, a tuberculin test, and a T-4 lymphocyte count were prepared for each patient. All 17 had an electrocardiogram, a radiography of the chest, and echocardiography, and 12 had pericardial needle aspiration. HIV pericarditis accounted for 50% of cases of pericarditis in the service. It was either dry or effusive with little fluid. Its clinical signs at the early stages of AIDS were retrosternal pain and pericardial friction rub. A search for anti-HIV antibodies may be negative at the early stages, but diagnostic errors can be avoided if the tuberculin test is negative a if an ELISA test is repeated at 3 week intervals. Pericarditis can be considered 1 of the minor signs of AIDS.

[African vaccine against AIDS]. / Vaccin Africain contre le SIDA.

PIP: In November 1987 the state commissar of information in Zaire announced that an Egyptian-Zairian research team had achieved good results in treatment of acquired immune deficiency syndrome (AIDS) using a new agent called M.M.1. Of the 19 AIDS patients given M.M.1, 7 died and 12 showed objective improvements in their health status. The group of 20 patients serving as controls received conventional AIDS therapy. All members of the control group died. A 3rd group of patients aged 18-51 years are currently receiving treatment with M.M.1. M.M.1 causes the fever to subside, fatigue to disappear, and cutaneous infections to diminish. 75% of the patients are cured of their cough and diarrhea. The researchers believe the drug to be an antiviral, atoxic agent capable of restoring the immune system. Composition of M.M.1 has not been revealed, but the researchers stated that its cost is a tiny fraction of that of other AIDS treatments.^ieng

Genomic diversity of Zairian HIV isolates: biological characteristics and clinical manifestation of HIV infection.

We describe here several African isolates of HIV, compare them to U.S.-European prototype isolates and to each other, correlate the number of isolates with serological results, and provide insights into the disease spectrum associated with HIV infection in Africa. Three of 25 healthy Zairian donors and 54 of 87 Zairian patients selected for specific pathology and hospitalized in the internal medicine department of the University Clinic of Kinshasa, Zaire, were HIV positive over a six month period in 1985 either by serum antibody (42 cases) or virus isolation (40 cases). The virus positive cases showed a decrease in number of T4 cells and interleukin-2 (IL2) production by mononuclear cells. Restriction endonuclease analysis of HIV sequences from these isolates showed that genomic diversity is also observed in the Zairian isolates but closely related viruses could also be found, similar to the spectrum of diversity among isolates obtained from the U.S. and Europe. A number of isolates (12 of 40) were obtained from serum antibody negative adults. These results are difficult to explain by viral antigenic diversity alone since hybridization with a HTLV-III-B (clone BH10) probe under stringent conditions indicated an overall high degree of relatedness. Rather, these results indicate that some African HIV infected patients fail to make detectable antibodies to HIV or the antibodies were bound in immune complexes not detectable by current techniques.