Despite decades of focused research, the field has yet to develop a prophylactic vaccine for HIV-1 infection. In the RV144 vaccine trial, nonneutralizing antibody responses were identified as a correlate for prevention of HIV acquisition. However, factors that predict the development of such antibodies are not fully elucidated. We sought to define the contribution of circulating T follicular helper (cTfh) subsets to the development of nonneutralizing antibodies in HIV-1 clade C infection. Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-gp41, -gp120, -p24, and -p17 antibodies were screened using a customized multivariate Luminex assay. Phenotypic and functional characterizations of cTfh cells were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed the differentiation of functional cTfh subsets toward increased Tfh1 ( = 0.02) and Tfh2 ( < 0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (which shares both Tfh1 and Tfh17 properties) ( = 0.01) and Tfh17 ( < 0.0001) subsets, compared to the subsets found in HIV-negative subjects. Interestingly, the frequencies of Tfh1 cells during acute infection (5.0 to 8.0 weeks postinfection) correlated negatively with the set point viral load ( = 0.03, Spearman rho [] = -60) and were predictive of p24-specific plasma IgG titers at 1 year of infection ( = 0.003, = 0.85). Taken together, our results suggest that the circulating Tfh1 subset plays an important role in the development of anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. These results have implications for vaccine studies aimed at inducing long-lasting anti-HIV antibody responses. The HIV epidemic in southern Africa accounts for almost half of the global HIV burden, with HIV-1 clade C being the predominant strain. It is therefore important to define immune correlates of clade C HIV control that might have implications for vaccine design in this region. T follicular helper (Tfh) cells are critical for the development of HIV-specific antibody responses and could play a role in viral control. Here we showed that the early induction of circulating Tfh1 cells during acute infection correlated positively with the magnitude of p24-specific IgG and was associated with a lower set point viral load. This study highlights a key Tfh cell subset that could limit HIV replication by enhancing antibody generation. This study underscores the importance of circulating Tfh cells in promoting nonneutralizing antibodies during HIV-1 infection.

p24 IgG1 levels independently predict viral control in HIV-1 clade C infection. Whether these responses contribute to direct antiviral control via the recruited killing of infected cells via the innate immune system or simply mark a qualitatively superior immune response to HIV, is uncertain, but highlights the role of p24-specific antibodies in control of clade C HIV-1 infection.

Background Schistosomiasis is a devastating parasitic disease. The mainstay of schistosomiasis control is by praziquantel treatment. The study aimed to determine benefits of annual chemotherapy of schistosomiasis on development of protective immunity in school children in a selected endemic rural area in Zimbabwe. Methods Urine specimens from 212 school children (7–13 years) were collected and examined to determine prevalence, intensity and reinfection of S.haematobium at baseline, 6 weeks and 2 years following annual rounds of praziquantel treatment . Blood samples from the participants were assayed for total and S. haematobium (Sh13)-specific antibodies before and 2 years after annual rounds of treatment. Results Annual treatment reduced the prevalence of S. haematobium infection ( p < 0.05) from 23.1% at baseline to 0.47% after 2 years. Overall cure rate was 97.8%. Intensity of infection declined (p < 0.05) from 15.9 eggs/10 ml urine at baseline to 2 eggs/10 ml urine. After two years, overall rate of reinfection was 0.96%. At baseline, total IgG4 was higher in S. haematobium -infected children ( p = 0.042) ,while all other immunoglobulins were within normal ranges. There was an increase in total IgG2 ( p = 0.044) levels and a decrease in total IgG4 ( p = 0.031) levels 2 years post-treatment; and no significant changes in other total immunoglobulins. Schistosoma -infected children at baseline showed an increase in anti- Sh 13 IgG1 ( p = 0.005) and a decrease in Sh 13 IgG4 levels ( p = 0.012) following treatment. Conclusion Annual praziquantel treatment delivered to school children over 2 years significantly reduce prevalence, intensity of infection and reinfection of S. haematobium infection. Treatment was also observed to cause a reduction in schistosome-specific blocking IgG4 and an increase in Schistosoma -specific protecting IgG1. Electronic supplementary material The online version of this article (10.1186/s12879-019-3811-z) contains supplementary material, which is available to authorized users.

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Word count:243) 24Despite decades of focused research, the field has yet to develop a prophylactic vaccine. In the 25 RV144 vaccine trial, non-neutralizing antibody responses were identified as a correlate for 26 prevention of HIV acquisition. However, factors that predict the development of such antibodies 27 are not fully elucidated. We sought to define the contribution of circulating T follicular helper 28 (cTfh) cell subsets to the development of non-neutralizing antibodies in HIV-1 clade C infection. 29Study participants were recruited from an acute HIV-1 clade C infection cohort. Plasma anti-30 gp41, -gp120, -p24 and -p17 antibodies were screened using a customized multivariate Luminex 31 assay. Phenotypic and functional characterization of cTfh were performed using HLA class II 32 tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C 33 infection skewed differentiation of functional cTfh subsets towards increased Tfh1 (p=0.02) and 34Tfh2 (p<0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (that shares both Tfh1 35 and Tfh17 properties) (p=0.01) and Tfh17 subsets (p<0.0001) compared to HIV negative 36 subjects. Interestingly, the frequencies of Tfh1 during acute infection (5.0-8.0 weeks post-37 infection) correlated negatively with set point viral load (p=0.03, r=-60) and were predictive of 38 p24-specific plasma IgG titers at one year of infection (p=0.003, r=0.85). Taken together, our 39 results suggest that circulating the Tfh1 subset plays an important role in the development of 40 anti-HIV antibody responses and contributes to HIV suppression during acute HIV-1 infection. 41 These results have implications for vaccine studies aimed at inducing long lasting anti-HIV 42 antibody responses. 43 44 45 3

Optimal methods for using dried blood spots (DBS) for population genetics-based studies have not been well-established. Using DBS stored for 8 years from 21 pregnant South African women we evaluated 3 methods of gDNA extraction with and without whole genome amplification (WGA) to characterize immune-related genes: Interleukin 10 (IL-10), Killer Immunoglobulin-like Receptors (KIR) and Human Leukocyte Antigen (HLA) class I. We found that the QIAamp DNA mini kit yielded the highest gDNA quality (p<0.05; Wilcoxon Signed Rank Test) with sufficient yield for subsequent analyses. In contrast, we found that WGA was not reliable for SSP-PCR analysis of KIR2DL1, KIR2DS1, KIR2DL5, and KIR2DL3 or high-resolution HLA genotyping using a sequence-based approach. We speculate that unequal template amplification by WGA under-represents gene repertoires determined by sequencing-based approaches.

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Objective: There is an increased risk of cases of direct and indirect morbidities as a result of stimulation of tissue-destructive inflammation caused by Schistosoma haematobium infection, hence the need to determine the levels of inflammatory markers in Schistosoma haematobium infected children and also determine the effect of repeated annual mass treatment on levels of interleukin-6 and acute phase proteins. Methodology: Urine specimens from 212 school children were collected and examined to determine prevalence of Schistosoma haematobium at baseline and 2 years following annual rounds of praziquantel treatment. Levels of 4 acute phase proteins were measured from serum samples from the participants using the magnetic bead-based immuno-assays at baseline and 2 years following praziquantel treatment. Sandwich enzyme-linked immunosorbent assay was used to determine levels of interleukin-6. Results: The overall pre-treatment prevalence of Schistosoma haematobium infection was 23.1% at baseline and 0.47% after 2 years of annual treatments. Schistosoma haematobium infected children had marginally higher levels of procalcitonin and tissue plasminogen activator before treatment though the difference of all three was not significant p>0.05 using Mann-Whitney non-parametric U test. Levels of ferritin and fibrinogen were lower in Schistosoma haematobium infected children before treatment, however the difference was also not significant p>0.05 using Mann-Whitney test. There was no association between infection status or interleukin-6 and the levels acute phase proteins p>0.05 for all acute phase proteins using the Mann-Whitney U test. Discussion and Conclusion: Findings from this study suggest no bearing of Schistosoma haematobium infection status on level of acute phase proteins before and after annual treatment with praziquantel. The extent of inflammation cannot be determined using ferritin, tissue plasminogen activator and fibrinogen. Levels of interleukin-6 did not have any bearing on levels of acute phase proteins. There is a need to explore other acute phase proteins as inflammatory markers in Schistosoma haematobium infection.