Augmentation of anti-simian immunodeficiency virus activity in CD8+ cells by neutralizing but not nonneutralizing antibodies in the acute phase

Yamamoto, Haruyuki; Iseda, Sumire; Nakane, Taku; Nomura, Takushi; Takahashi, Naofumi; Seki, Sayuri; Nakamura, Midori; Ishii, Hiroshi; Matano, Tetsuro

doi:10.1097/qad.0000000000001221

Cited by 5 publications

(4 citation statements)

References 22 publications

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“…Studies undertaken in macaques with early SIV infection have shown that infusions of acute phase SIV Env-specific IgG antibodies with neutralizing activity suppress SIV replication for up to 2 years and that this effect is associated with an increased uptake of SIV by cDCs and an enhancement of SIV-specific CD4 + and CD8 + T-cell responses (12, 122, 123). Enhancing HIV-1 uptake by cDCs is also a possible explanation for the observation that a single infusion of the HIV-1 Env CD4 binding site (CD4bs)-specific hMAb 3BNC117 augmented production of HIV-1 Env-specific IgG antibodies with neutralizing activity (11).…”

Section: Functional Effects Of Igg Antibody Responses Against Hiv-1mentioning

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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Section: Functional Effects Of Igg Antibody Responses Against Hiv-1mentioning

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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“…Late-phase dominance of a single epitopespecific CD8 R T-cell response in passive NAbinduced simian immunodeficiency virus control In our model of passive NAb-based SIV mac239 control, macaques receiving a single NAb infusion contained SIV replication. Acute-phase CD8 þ cells showed increased viral suppressive activity in vitro against wild-type and CTL escape mutant viruses following elevated dendritic cellassociated viral loads, suggesting CTL broadening by NAbenhanced CTL cross-priming [13,15,17,19]. We detected immunodominant epitope-specific CTL responses at year 2, while it was left unidentified when this population developed [13].…”

Section: Resultsmentioning

confidence: 80%

“…This occurred under NAb-boosted T-cell responses, including elevated Gag-specific CD4 þ T-cell polyfunctionality and enhanced in-vitro CD8 þcell virus-suppressive activity following rapid viral RNA accumulation in dendritic cells. When nonneutralizing anti-SIV IgG with cell-dependent antiviral activity was similarly infused, there was no CD8 þ -cell augmentation and viral control [18,19]. During this control, a subpopulation of epitope-specific CTLs showed low phosphorylated AMPK (pAMPK) expression [13].…”

Section: Introductionmentioning

confidence: 99%

Late-phase dominance of a single epitope-specific CD8+ T-cell response in passive neutralizing antibody-infused simian immunodeficiency virus controllers

Kanno

Hau

Kurokawa

et al. 2021

Aids

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Objective: Analysis of the quantity and quality of epitope-specific CD8 þ T-cell responses is crucial for understanding the mechanism of HIV/simian immunodeficiency virus (SIV) replication control. We have previously shown that acute-phase passive infusion of neutralizing antibodies (NAbs) results in augmented broad T-cell responses and robust SIV mac239 control in rhesus macaques. Analyzing long-term dynamics of CD8 þ T-cell responses in these SIV controllers provides important insights into designing lasting anti-HIV immunity.Design: We analyzed dynamics and metabolic/functional profiles of SIV-specific CD8 þ T-cell responses in rhesus macaques that controlled SIV mac239 replication following acute-phase passive NAb infusion.Methods: SIV epitope-specific CD8 þ T-cell responses in peripheral blood at multiple chronic-phase time points were investigated in four passive NAb-infused SIV controllers. In particular, expression patterns of Eomesodermin (Eomes), phosphorylated AMP kinase (pAMPK), CD28 and programmed death-1 (PD-1) were examined.Results: In the NAb-infused SIV controllers, a single epitope-specific CD8 þ T-cell response detected from acute infection and maintaining low levels up to year 1 showed a surge thereafter, up to year 2 postchallenge. Retention of an effector-skewed and unexhausted Eomes-high/pAMPK-low/CD28-negative/PD-1-low subpopulation in these epitope-specific CD8 þ T cells implicated their front-line commitment in residual viral replication control. Conclusion:In long-term SIV control following acute-phase passive NAb infusion, a single-epitope, high-quality CTL response was dominantly induced in the chronic phase. These results likely describe one favorable pattern of immunodominant epitope-specific CD8 þ T-cell preservation and suggest the importance of incorporating metabolic marker signatures for understanding NAb/T-cell synergism-based HIV/SIV control .

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“…Similarly, in acute-phase infection, polyclonal non-NAb infusion at day 7 achieved no SIV viremia control in our model (Nakane et al, 2013). We very recently compared viral suppressive activity in our aforementioned polyclonal NAb- and non-NAb-infused rhesus macaques, and found that CD8 + -cell viral suppressive activity is selectively enhanced in NAb-infused but not in non-NAb-infused animals (Yamamoto et al, 2016). This means that in addition to the availability of direct virus neutralization, such property of antiviral antibodies may also directly affect modulation patterns of cellular immune responses and further impact disease prognosis.…”

Section: Requisite Of Neutralizing Activity In Passive Antibody-basedmentioning

confidence: 99%

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization

Yamamoto

Matano

2016

Front. Microbiol.

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Neutralizing antibody (NAb) responses are promising immune effectors for control of human immunodeficiency virus (HIV) infection. Protective activity and mechanisms of immunodeficiency virus-specific NAbs have been increasingly scrutinized in animals infected with simian immunodeficiency virus (SIV), chimeric simian/human immunodeficiency virus (SHIV) and related viruses. Studies on such models have unraveled a previously underscored protective potential against in vivo immunodeficiency virus replication. Pre-challenge NAb titers feasibly provide sterile protection from SIV/SHIV infection by purging the earliest onset of viral replication and likely modulate innate immune cell responses. Sufficient sub-sterile NAb titers after established infection also confer dose-dependent reduction of viremia, and in certain earlier time frames augment adaptive immune cell responses and even provide rebound-free viral control. Here, we provide an overview of the obtained patterns of SIV/SHIV protection and viral control by various types of NAb passive immunizations and discuss how these notions may be extrapolated to NAb-based clinical control of HIV infection.

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Augmentation of anti-simian immunodeficiency virus activity in CD8+ cells by neutralizing but not nonneutralizing antibodies in the acute phase

Cited by 5 publications

References 22 publications

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

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

Late-phase dominance of a single epitope-specific CD8+ T-cell response in passive neutralizing antibody-infused simian immunodeficiency virus controllers

Patterns of HIV/SIV Prevention and Control by Passive Antibody Immunization

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