Vaccine-Induced T Cells Control Reversion of AIDS Virus Immune Escape Mutants

Fernandez, Caroline S.; Smith, Miranda; Batten, C. Jane; Rose, Robert De; Reece, Jeanette C.; Rollman, Erik; Venturi, Vanessa; Davenport, Miles P.; Kent, Stephen J.

doi:10.1128/jvi.02193-06

Cited by 32 publications

(43 citation statements)

References 26 publications

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“…In the absence of immune pressure, the advantage of the EM virus (i.e., reduced immune recognition) is lost, and the reduced replicative capacity of EM virus compared to that of the wild-type (WT) virus leads to a reversion from the EM to the WT virus. This has been observed in vitro (15,27), as well as in both humans and macaques who lack the major histocompatibility complex (MHC) molecules required for the recognition of the WT epitope (10,14,22). A phase of transient reversion followed by reescape has also been observed early after infection in individuals bearing the required MHC, as at least some growth of the WT virus is required to induce an immune response to the epitope (1,10).…”

Section: Infections With Human Immunodeficiency Virus (Hiv) and The Cmentioning

confidence: 89%

“…This has been observed in vitro (15,27), as well as in both humans and macaques who lack the major histocompatibility complex (MHC) molecules required for the recognition of the WT epitope (10,14,22). A phase of transient reversion followed by reescape has also been observed early after infection in individuals bearing the required MHC, as at least some growth of the WT virus is required to induce an immune response to the epitope (1,10). This dynamic of immune escape and reversion within the infected individual leads to the transmission and persistence of both WT and EM virus in the human population (28).…”

Section: Infections With Human Immunodeficiency Virus (Hiv) and The Cmentioning

confidence: 99%

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CD4 ⁺ Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

Petravic

Loh

Kent

et al. 2008

J Virol

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Infections with human immunodeficiency virus (HIV) and the closely related monkey viruses simian-human immunodeficiency virus (SHIV) and simian immunodeficiency virus (SIV) are characterized by progressive waves of immune responses, followed by viral mutation and "immune escape." However, escape mutation usually leads to lower replicative fitness, and in the absence of immune pressure, an escape mutant (EM) virus "reverts" to the wild-type phenotype. Analysis of the dynamics of immune escape and reversion has suggested it is a mechanism for identifying the immunogens best capable of controlling viremia. We have analyzed and modeled data of the dynamics of wild-type (WT) and EM viruses during SHIV infection of macaques. Modeling suggests that the dynamics of reversion and immune escape should be determined by the availability of target cells for infection. Consistent with this suggestion, we find that the rate of reversion of cytotoxic T-lymphocyte (CTL) EM virus strongly correlates with the number of CD4 ؉ T cells available for infection. This phenomenon also affects the rate of immune escape, since this rate is determined by the balance of CTL killing and the WT fitness advantage. This analysis predicts that the optimal timing for the selection of immune escape variants will be immediately after the peak of viremia and that the development of escape variants at later times will lead to slower selection. This has important implications for comparative studies of immune escape and reversion in different infections and for identifying epitopes with high fitness cost for use as vaccine targets.

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Section: Infections With Human Immunodeficiency Virus (Hiv) and The Cmentioning

confidence: 89%

Section: Infections With Human Immunodeficiency Virus (Hiv) and The Cmentioning

confidence: 99%

CD4 ⁺ Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

Petravic

Loh

Kent

et al. 2008

J Virol

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“…This reversion is observed commonly with CTL mutations (16). Note that this reversion of ADCC-induced mutations may be transient if the recipient subsequently mounts ADCC responses to the same epitope (23). Longitudinal analyses of HIV strains in donor-recipient pairs for reversion of ADCCinduced mutations will be of substantial interest.…”

Section: Discussionmentioning

confidence: 99%

Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure

Chung

Isitman

Navis

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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130

132

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Effective immunity to HIV is poorly understood. In particular, a role for antibody-dependent cellular cytotoxicity (ADCC) in controlling HIV is controversial. We hypothesized that significant pressure from HIV-specific ADCC would result in immune-escape variants. A series of ADCC epitopes in HIV-infected subjects to specific consensus strain HIV peptides were mapped using a flow cytometric assay for natural killer cell activation. We then compared the ADCC responses to the same peptide epitope derived from the concurrent HIV sequence(s) expressed in circulating virus. In 9 of 13 epitopes studied, ADCC antibodies were unable to recognize the concurrent HIV sequence. Our studies suggest ADCC responses apply significant immune pressure on the virus. This result has implications for the induction of ADCC responses by HIV vaccines.natural killer cells | viral evolution | neutralizing antibody

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“…A substantial delay of activation, expansion, and potentially cytolytic function of these cells exists following virus challenge (19,20). We recently showed that the baseline prechallenge levels, and rates of expansion, of recombinant DNA and poxvirus vaccine-induced SIV-specific T cells correlate with control of wild-type virus at an immunodominant Gag epitope (21). Memory CD4 ϩ T cells are irreparably lost during the early days of acute SIV infection of macaques (22), before the efficient expansion of CD8 ϩ T cells generated by typical vector-based vaccines.…”

Section: R Esearch Shows That Cd8 ϩ T Cells Help Partially Control Himentioning

confidence: 99%

Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies

Rollman

Smith

Brööks

et al. 2007

The Journal of Immunology

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Both the magnitude and function of vaccine-induced HIV-specific CD8+ CTLs are likely to be important in the outcome of infection. We hypothesized that rapid cytolysis by CTLs may facilitate control of viral challenge. Release kinetics of the cytolytic effector molecules granzyme B and perforin, as well as the expression of the degranulation marker CD107a and IFN-γ were simultaneously studied in SIV Gag164–172 KP9-specific CD8+ T cells from Mane-A*10+ pigtail macaques. Macaques were vaccinated with either prime-boost poxvirus vector vaccines or live-attenuated SIV vaccines. Prime-boost vaccination induced Gag-specific CTLs capable of only slow (after 3 h) production of IFN-γ and with limited (<5%) degranulation and granzyme B release. Vaccination with live-attenuated SIV resulted in a rapid cytolytic profile of SIV-specific CTLs with rapid (<0.5 h) and robust (>50% of tetramer-positive CD8+ T cells) degranulation and granzyme B release. The cytolytic phenotype following live-attenuated SIV vaccinations were similar to that associated with the partial resolution of viremia following SIVmac251 challenge of prime-boost-vaccinated macaques, albeit with less IFN-γ expression. High proportions of KP9-specific T cells expressed the costimulatory molecule CD28 when they exhibited a rapid cytolytic phenotype. The delayed cytolytic phenotype exhibited by standard vector-based vaccine-induced CTLs may limit the ability of T cell-based HIV vaccines to rapidly control acute infection following a pathogenic lentiviral exposure.

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Vaccine-Induced T Cells Control Reversion of AIDS Virus Immune Escape Mutants

Cited by 32 publications

References 26 publications

CD4 ⁺ Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

CD4 ⁺ Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure

Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies

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Vaccine-Induced T Cells Control Reversion of AIDS Virus Immune Escape Mutants

Cited by 32 publications

References 26 publications

CD4 + Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

CD4 + Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

Immune escape from HIV-specific antibody-dependent cellular cytotoxicity (ADCC) pressure

Killing Kinetics of Simian Immunodeficiency Virus-Specific CD8+ T Cells: Implications for HIV Vaccine Strategies

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CD4 ⁺ Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo

CD4 ⁺ Target Cell Availability Determines the Dynamics of Immune Escape and Reversion In Vivo