Highly Efficient Neutralization by Plasma Antibodies from Human Immunodeficiency Virus Type-1 Infected Individuals on Antiretroviral Drug Therapy

Andrabi, Raiees; Makhdoomi, Muzamil Ashraf; Kumar, Rajesh; Bala, Manju; Parray, Hilal Ahmad; Gupta, Arjun; Kotnala, Ankita; Velpandian, Thirumurthy; Luthra, Kalpana

doi:10.1007/s10875-014-0010-y

Cited by 7 publications

(9 citation statements)

References 56 publications

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“…The identification of potential humoral immune-mediated mechanisms associated with the control of HIV viremia and the nonprogressive disease status in these individuals may lead to new approaches for preventing and managing HIV disease. It is generally agreed that the persistence of humoral responses to HIV in infected individuals, even those whose virus replication is well controlled by ART, is due to low levels of virus replication that continually stimulate B-cell responses [35][36][37]. However, the precise role of the residual viral burden in maintaining HIV-specific immune responses in ECs and the relationship of this interplay of humoral immunity and viral burden in ECs as compared to that in HIV-infected individuals who require ART to control viral replication are unclear.…”

Section: Discussionmentioning

confidence: 99%

Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens

Buckner¹,

Kardava²,

Zhang³

et al. 2016

J Infect Dis.

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Human immunodeficiency virus (HIV)-specific B-cell responses in infected individuals are maintained by active HIV replication. Suppression of viremia by antiretroviral therapy (ART) leads to quantitative and qualitative changes that remain unclear. Accordingly, B-cell responses were investigated in elite controllers (ECs), who maintain undetectable HIV levels without ART, and in individuals whose viremia was suppressed by ART. Despite a higher HIV burden in the ART group, compared with the EC group, frequencies of HIV-specific B cells were higher in the EC group, compared with those in the ART group. However, the initiation of ART in several ECs was associated with reduced frequencies of HIV-specific B cells, suggesting that responses are at least in part sustained by HIV replication. Furthermore, B-cell responses to tetanus toxin but not influenza hemagglutinin in the ART group were lower than those in the EC group. Thus, the superior HIV-specific humoral response in ECs versus ART-treated individuals is likely due to a more intact humoral immune response in ECs and/or distinct responses to residual HIV replication.

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Section: Discussionmentioning

confidence: 99%

Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens

Buckner¹,

Kardava²,

Zhang³

et al. 2016

J Infect Dis.

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“…Introduction of ART results in a decline in HIV-1 Env-specific IgG antibodies that elicit NK cell activation or opsonization of HIV-1 gp140-coated beads and phagocytosis by monocytes (THP-1 cells) (158). With regard to neutralization activity, it has been reported that all HIV patients receiving long-term ART exhibit plasma HIV-1 Env-specific antibodies with neutralizing activity against at least one heterologous HIV-1 (159). However, ART does not usually increase HIV-1 Env-specific antibodies with neutralizing activity against autologous HIV-1 (160, 161).…”

Section: Effects Of Hiv-1 Infection and Art On Hiv-1-specific Igg Antmentioning

confidence: 99%

Antiviral Functions of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific IgG Antibodies: Effects of Antiretroviral Therapy and Implications for Therapeutic HIV-1 Vaccine Design

et al. 2017

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Contemporary antiretroviral therapy (ART) is effective and tolerable for long periods of time but cannot eradicate human immunodeficiency virus type 1 (HIV-1) infection by either elimination of viral reservoirs or enhancement of HIV-1-specific immune responses. Boosting “protective” HIV-1-specific immune responses by active or passive immunization will therefore be necessary to control or eradicate HIV-1 infection and is currently the topic of intense investigation. Recently reported studies conducted in HIV patients and non-human primate (NHP) models of HIV-1 infection suggest that HIV-1-specific IgG antibody responses may contribute to the control of HIV-1 infection. However, production of IgG antibodies with virus neutralizing activity by vaccination remains problematic and while vaccine-induced natural killer cell-activating IgG antibodies have been shown to prevent the acquisition of HIV-1 infection, they may not be sufficient to control or eradicate established HIV-1 infection. It is, therefore, important to consider other functional characteristics of IgG antibody responses. IgG antibodies to viruses also mediate opsonophagocytic antibody responses against virions and capsids that enhance the function of phagocytic cells playing critical roles in antiviral immune responses, particularly conventional dendritic cells and plasmacytoid dendritic cells. Emerging evidence suggests that these antibody functions might contribute to the control of HIV-1 infection. In addition, IgG antibodies contribute to the intracellular degradation of viruses via binding to the cytosolic fragment crystallizable (Fc) receptor tripartite motif containing-21 (TRIM21). The functional activity of an IgG antibody response is influenced by the IgG subclass content, which affects binding to antigens and to Fcγ receptors on phagocytic cells and to TRIM21. The IgG subclass content and avidity of IgG antibodies is determined by germinal center (GC) reactions in follicles of lymphoid tissue. As HIV-1 infects cells in GCs and induces GC dysfunction, which may persist during ART, strategies for boosting HIV-1-specific IgG antibody responses should include early commencement of ART and possibly the use of particular antiretroviral drugs to optimize drug levels in lymphoid follicles. Finally, enhancing particular functions of HIV-1-specific IgG antibody responses by using adjuvants or cytokines to modulate the IgG subclass content of the antibody response might be investigated in NHP models of HIV-1 infection and during trials of therapeutic vaccines in HIV patients.

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“…Antiretroviral therapy has played a critical role in treating HIV-1 infected individuals by reducing viraemia and delaying disease progression [2]. Early initiation of cART, based on the WHO recommendations of test and treat [18], has shown beneficial effects in both adults [24] and in children who have acquired HIV-1 infection by vertical transmission [2,10]. At an early stage of infection, the cART may potentially retard the dissemination of infection and limit the establishment of latent viral reservoirs, and thereby help restore and prevent further damage to the immune system.…”

Section: Discussionmentioning

confidence: 99%

“…The increase in breadth and potency of nAbs post-cART initiation in this cohort of infants suggests the beneficial effect of early initiation of cART towards development of HIV-1 cross-neutralizing bnAbs in these children (infants/toddlers). This could perhaps be attributed to the reduction in viraemia that, in turn, may have favoured the survival of selective HIV-1 specific B cells that undergo affinity maturation and evolve into bnAbs [24]. The impact on cART on the development of HIV-1 bnAb generating B cells and their characteristics needs to be studied.…”

Section: Discussionmentioning

confidence: 99%

Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children

Kumar

Batra

Singh

et al. 2020

Journal of General Virology

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Protective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression. Herein, we longitudinally evaluated the effect of cART on HIV-1 specific plasma ADCC and nAb responses in a cohort of 20 perinatally HIV-1 subtype-C infected infants and children ≤2 years of age, pre-cART and up to 1 year post-cART initiation. Significant reductions in HIV-1 specific plasma ADCC responses to subtype-C and subtype-B viruses and improvement in HIV-1 neutralization were observed in HIV-1 infected children 1 year post-cART initiation. A positive correlation between reduction in viral load and the loss of ADCC response was observed. This study provides information aiding the understanding of the effects of early initiation of cART on antibody effector functions and viral neutralization in HIV-1 infected children, which needs to be further evaluated in large cohorts of HIV-1 infected children on cART to plan future intervention strategies.

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Highly Efficient Neutralization by Plasma Antibodies from Human Immunodeficiency Virus Type-1 Infected Individuals on Antiretroviral Drug Therapy

Cited by 7 publications

References 56 publications

Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens

Maintenance of HIV-Specific Memory B-Cell Responses in Elite Controllers Despite Low Viral Burdens

Antiviral Functions of Human Immunodeficiency Virus Type 1 (HIV-1)-Specific IgG Antibodies: Effects of Antiretroviral Therapy and Implications for Therapeutic HIV-1 Vaccine Design

Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children

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