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PULMONARY TUBERCULOSIS DISEASE ENHANCES HIV-1 ANTIBODY RESPONSES
Bukola Adeoye1, Alex J. Olson2, Lydia Nakiyingi3, Yukari C. Manabe4, Karen R. Jacobson2, Jerrold Ellner5, Manish Sagar1
1Boston University, Boston, MA, USA,2Boston Medical Center, Boston, MA, USA,3Makerere University College of Health Sciences, Kampala, Uganda,4Johns Hopkins University School of Medicine, Baltimore, MD, USA,5Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA
Mycobacterium tuberculosis (TB) is an integral component of complete Freunds adjuvant which is known to augment antibody production. We hypothesized that active TB disease enhances the development of HIV-1 broadly neutralizing antibodies (bnAbs) in people living with HIV-1.
We compared anti-HIV-1 antibody response among treatment-naive plasma samples from 15 HIV-1 patients with active pulmonary TB (HIV-1/TB) and 16 HIV-1 only infected individuals. Ability to inhibit 12 different tier 1 and 2 HIV-1 variants of diverse subtypes in the TZM-bl neutralization assay was used to estimate a neutralization breadth and potency (BP) score. Total IgG and cytokine levels were estimated using multiplex Luminex based assays. Neutralization heatmaps were used to identify potential targeted HIV-1 envelope epitopes. Comparisons were done using the Wilcoxon rank-sum and Fischer’s exact tests.
HIV-1/TB and HIV-1 only infected individuals had similar baseline plasma virus levels (p= 0.33) and CD4 counts (p= 0.40). HIV-1/TB individuals had a significantly higher BP score (0.59 0.05, range 0.34-0.98) than the HIV-1 only group (0.43 0.02, range 0.25-0.59, p= 0.006). Four of the HIV-1/TB but none of the HIV-1 only infected individuals had a similar or higher BP score as that observed among 2nd generation bnAbs (BP score range 0.71-0.98, p= 0.04). Neutralization BP score correlated with the total plasma IgG (r = 0.51, p= 0.003), but not with baseline viral load, absolute CD4 count, IL-6, soluble CD163 or MCP-1 concentrations. After completing TB treatment and starting HIV-1 therapy, HIV-1/TB (0.68 0.07, n= 6, range 0.28-0.88) as compared to HIV-1 only infected subjects (0.57 0.07, n= 8, range 0.34-0.82) still had higher neutralizing capacity, but the difference was not statistically significant (p= 0.56). The plasma activity of the 4 HIV-1/TB individuals with high baseline BP score clustered with CD4 binding site and membrane-proximal external region targeting bnAbs.
Our results suggest that active TB enhances anti-HIV-1 antibody response, possibly leading to the emergence of bnAbs that target conserved envelope domains. Dissecting mechanisms that account for the enhanced HIV-1 neutralization in HIV-1 cases with TB could be leveraged in the generation of a more effective humoral response in HIV-1 vaccination and treatment.