Reduction of anti-HIV antibody responses in subjects receiving antiretroviral therapy during chronic HIV-1 infection

2020 ◽  
Vol 128 ◽  
pp. 104414
Author(s):  
Yuanhao Liang ◽  
Linghua Li ◽  
Jingwei Shui ◽  
Fengyu Hu ◽  
Haiying Wang ◽  
...  
2018 ◽  
Author(s):  
Omolara Baiyegunhi ◽  
Bongiwe Ndlovu ◽  
Funsho Ogunshola ◽  
Nasreen Ismail ◽  
Bruce D. Walker ◽  
...  

AbstractDespite decades of focused research, the field has yet to develop a prophylactic vaccine. In the RV144 vaccine trial, non-neutralizing 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) cell subsets to the development of non-neutralizing 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 characterization of cTfh were performed using HLA class II tetramers and intracellular cytokine staining. In this study, we found that acute HIV-1 clade C infection skewed differentiation of functional cTfh subsets towards increased Tfh1 (p=0.02) and Tfh2 (p<0.0001) subsets, with a concomitant decrease in overall Tfh1-17 (that shares both Tfh1 and Tfh17 properties) (p=0.01) and Tfh17 subsets (p<0.0001) compared to HIV negative subjects. Interestingly, the frequencies of Tfh1 during acute infection (5.0-8.0 weeks post-infection) correlated negatively with set point viral load (p=0.03, r=-60) and were predictive of p24-specific plasma IgG titers at one year of infection (p=0.003, r=0.85). Taken together, our results suggest that circulating the 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.ImportanceThe 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 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 non-neutralizing antibodies during HIV-1 infection.


2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Kathryn E. Stephenson ◽  
George H. Neubauer ◽  
Christine A. Bricault ◽  
Jennifer Shields ◽  
Madeleine Bayne ◽  
...  

Abstract The examination of antibody responses in human immunodeficiency virus (HIV)-1-infected individuals in the setting of antiretroviral treatment (ART) interruption can provide insight into the evolution of antibody responses during viral rebound. In this study, we assessed antibody responses in 20 subjects in AIDS Clinical Trials Group A5187, wherein subjects were treated with antiretroviral therapy during acute/early HIV-1 infection, underwent analytic treatment interruption, and subsequently demonstrated viral rebound. Our data suggest that early initiation of ART arrests the maturation of HIV-1-specific antibody responses, preventing epitope diversification of antibody binding and the development of functional neutralizing capacity. Antibody responses do not appear permanently blunted, however, because viral rebound triggered the resumption of antibody maturation in our study. We also found that antibody responses measured by these assays did not predict imminent viral rebound. These data have important implications for the HIV-1 vaccine and eradication fields.


2001 ◽  
Vol 75 (9) ◽  
pp. 4413-4419 ◽  
Author(s):  
Zheng Fan ◽  
Xiao-Li Huang ◽  
Luann Borowski ◽  
John W. Mellors ◽  
Charles R. Rinaldo

ABSTRACT We demonstrate that dendritic cells loaded in vitro with human immunodeficiency virus type 1 (HIV-1) protein-liposome complexes activate HLA class I-restricted anti-HIV-1 cytotoxic T-lymphocyte and gamma interferon (IFN-γ) responses in autologous CD8+ T cells from late-stage HIV-1-infected patients on prolonged combination drug therapy. Interleukin-12 enhanced this effect through an interleukin-2- and IFN-γ-mediated pathway. This suggests that dendritic cells from HIV-1-infected persons can be engineered to evoke stronger anti-HIV-1 CD8+ T-cell reactivity as a strategy to augment antiretroviral therapy.


PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160192 ◽  
Author(s):  
Sulggi A. Lee ◽  
Peter Bacchetti ◽  
Nicolas Chomont ◽  
Remi Fromentin ◽  
Sharon R. Lewin ◽  
...  

2005 ◽  
Vol 110 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Rebekah L. Puls ◽  
Sean Emery

Although effective in reducing mortality, current antiretroviral therapy for HIV infection involves complex and expensive drug regimens that are toxic and difficult to take. Eradication of HIV reservoirs is not possible with existing therapies. The concept of therapeutic vaccination has been investigated to increase the potency and breadth of anti-HIV immune responses in order to delay or reduce antiretroviral therapy use. A variety of approaches targeted to both cell- and antibody-mediated immunity have been developed, including whole inactivated HIV-1, protein subunits and synthetic peptides, DNA vaccines and a number of viral vectors expressing HIV-1. These investigations have occurred in the absence of a clear understanding of disease pathogenesis or the correlates of protective immunity. At this time, there is no licensed therapeutic vaccine for any viral disease, including HIV; however, this review will consider recent progress in the field and summarize the challenges faced in the development of a therapeutic HIV vaccine.


Vaccine ◽  
2016 ◽  
Vol 34 (19) ◽  
pp. 2225-2232 ◽  
Author(s):  
Frank Y. Tung ◽  
Jack K. Tung ◽  
Suresh Pallikkuth ◽  
Savita Pahwa ◽  
Margaret A. Fischl

Retrovirology ◽  
2016 ◽  
Vol 13 (1) ◽  
Author(s):  
Eunsil Choi ◽  
Chad J. Michalski ◽  
Seung Ho Choo ◽  
Gyoung Nyoun Kim ◽  
Elizabeth Banasikowska ◽  
...  

HIV Medicine ◽  
2006 ◽  
Vol 7 (8) ◽  
pp. 514-519 ◽  
Author(s):  
L Adalid-Peralta ◽  
L Grangeot-Keros ◽  
A Rudent ◽  
N Ngo-Giang-Huong ◽  
R Krzysiek ◽  
...  

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