We have examined the exposure and conservation of antigenic epitopes on the surface envelope glycoproteins (gp120 and gp41) of 26 intact, native, primary human immunodeficiency virus type 1 (HIV-1) group M virions of clades A to H. For this, 47 monoclonal antibodies (MAbs) derived from HIV-1-infected patients were used which were directed at epitopes of gp120 (specifically V2, C2, V3, the CD4-binding domain [CD4bd], and C5) and epitopes of gp41 (clusters I and II). Of the five regions within gp120 examined, MAbs bound best to epitopes in the V3 and C5 regions. Only moderate to weak binding was observed by most MAbs to epitopes in the V2, C2, and CD4bd regions. Two anti-gp41 cluster I MAbs targeted to a region near the tip of the hydrophilic immunodominant domain bound strongly to >90% of isolates tested. On the other hand, binding of anti-gp41 cluster II MAbs was poor to moderate at best. Binding was dependent on conformational as well as linear structures on the envelope proteins of the virions. Further studies of neutralization demonstrated that MAbs that bound to virions did not always neutralize but all MAbs that neutralized bound to the homologous virus. This study demonstrates that epitopes in the V3 and C5 regions of gp120 and in the cluster I region of gp41 are well exposed on the surface of intact, native, primary HIV-1 isolates and that cross-reactive epitopes in these regions are shared by many viruses from clades A to H. However, only a limited number of MAbs to these epitopes on the surface of HIV-1 isolates can neutralize primary isolates.

BackgroundHuman immunodeficiency virus (HIV) and malaria co-infection may present worse health outcomes in the tropics. Information on HIV/malaria co-infection effect on immune-hematological profiles is critical for patient care and there is a paucity of such data in Nigeria.ObjectiveTo evaluate immune-hematological profiles among HIV infected patients compared to HIV/malaria co-infected for ART management improvement.MethodsThis was a cross sectional study conducted at Infectious Disease Hospital, Kano. A total of 761 consenting adults attending ART clinic were randomly selected and recruited between June and December 2015. Participants’ characteristics and clinical details including two previous CD4 counts were collected. Venous blood sample (4ml) was collected in EDTA tube for malaria parasite diagnosis by rapid test and confirmed with microscopy. Hematological profiles were analyzed by Sysmex XP-300 and CD4 count by Cyflow cytometry. Data was analyzed with SPSS 22.0 using Chi-Square test for association between HIV/malaria parasites co-infection with age groups, gender, ART, cotrimoxazole and usage of treated bed nets. Mean hematological profiles by HIV/malaria co-infection and HIV only were compared using independent t-test and mean CD4 count tested by mixed design repeated measures ANOVA. Statistical significant difference at probability of <0.05 was considered for all variables.ResultsOf the 761 HIV infected, 64% were females, with a mean age of ± (SD) 37.30 (10.4) years. Prevalence of HIV/malaria co-infection was 27.7% with Plasmodium falciparum specie accounting for 99.1%. No statistical significant difference was observed between HIV/malaria co-infection in association to age (p = 0.498) and gender (p = 0.789). A significantly (p = 0.026) higher prevalence (35.2%) of co-infection was observed among non-ART patients compared to (26%) ART patients. Prevalence of co-infection was significantly lower (20.0%) among cotrimoxazole users compared to those not on cotrimoxazole (37%). The same significantly lower co-infection prevalence (22.5%) was observed among treated bed net users compared to those not using treated bed nets (42.9%) (p = 0.001). Out of 16 hematology profiles evaluated, six showed significant difference between the two groups (i) packed cell volume (p = <0.001), (ii) mean cell volume (p = 0.005), (iii) mean cell hemoglobin concentration (p = 0.011), (iv) absolute lymphocyte count (p = 0.022), (v) neutrophil percentage count (p = 0.020) and (vi) platelets distribution width (p = <0.001). Current mean CD4 count cell/μl (349±12) was significantly higher in HIV infected only compared to co-infected (306±17), (p = 0.035). A significantly lower mean CD4 count (234.6 ± 6.9) was observed among respondents on ART compared to non-ART (372.5 ± 13.2), p<0.001, mean difference = -137.9).ConclusionThe study revealed a high burden of HIV and malaria co-infection among the studied population. Co-infection was significantly lower among patients who use treated bed nets as well as cotrimoxazole chemotherapy and...

In order to protect against organisms that exhibit significant genetic variation, polyvalent vaccines are needed. Given the extreme variability of human immunodeficiency virus type 1 (HIV-1), it is probable that a polyvalent vaccine will also be needed for protection from this virus. However, to understand how to construct a polyvalent vaccine, serotypes or immunotypes of HIV must be identified. In the present study, we have examined the immunologic relatedness of intact, native HIV-1 primary isolates of group M, clades A to H, with human monoclonal antibodies (MAbs) directed at epitopes in the V3, C5, and gp41 cluster I regions of the envelope glycoproteins, since these regions are well exposed on the virion surface. Multivariate analysis of the binding data revealed three immunotypes of HIV-1 and five MAb groups useful for immunotyping of the viruses. The analysis revealed that there are fewer immunotypes than genotypes of HIV and that clustering of the isolates did not correlate with either genotypes, coreceptor usage (CCR5 and CXCR4), or geographic origin of the isolates. Further analysis revealed distinct MAb groups that bound preferentially to HIV-1 isolates belonging to particular immunotypes or that bound to all three immunotypes; this demonstrates that viral immunotypes identified by mathematical analysis are indeed defined by their immunologic characteristics. In summary, these results indicate (i) that HIV-1 immunotypes can be defined, (ii) that constellations of epitopes that are conserved among isolates belonging to each individual HIV-1 immunotype exist and that these distinguish each of the immunotypes, and (iii) that there are also epitopes that are routinely shared by all immunotypes.

We have used a virus-binding assay to examine conformational changes that occur when soluble CD4 (sCD4) binds to the surface of intact, native, primary human immunodeficiency virus type 1 virions. The isolates examined belong to seven genetic clades (A to H) and are representative of syncytium-inducing and nonsyncytium-inducing phenotypes. Conformational changes in epitopes in the C2, V2, V3, C5, and CD4 binding domain (CD4bd) of gp120 and the cluster I and II regions of gp41 of these viruses were examined using human monoclonal antibodies that are directed at these regions. The studies revealed that sCD4 binding causes a marked increase in exposure of epitopes in the V3 loop, irrespective of the clade or the phenotype of the virus. Sporadic increases in exposure were observed in some epitopes in the V2 region, while no changes were observed in the C2, C5, or CD4bd of gp120 or the cluster I and II regions of gp41.

We have documented a wide range of HIV prevalences among rural villages of Cameroon. Age, marital status (in women) and sexual risk factors appear to be associated with HIV infection in this setting.