Effects of Antibody on Viral Kinetics in Simian/Human Immunodeficiency Virus Infection: Implications for Vaccination

Department of Haematology, Prince of Wales Hospital and Centre for Vascular Research, University of New South Wales, Kensington, New South Wales 2052, Australia.
Journal of Virology (Impact Factor: 4.44). 06/2004; 78(10):5520-2. DOI: 10.1128/JVI.78.10.5520-5522.2004
Source: PubMed


Passive antibody treatment of macaques prior to simian/human immunodeficiency virus infection produces “sterilizing immunity”
in some animals and long-term reductions in viral loads in others. Analysis of viral kinetics suggests that antibody mediates
sterilizing immunity by its effects on the initial viral inoculum. By contrast, reduction in peak viral load later in infection
prevents CD4 depletion and contributes to long-term viral control.

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    • "Understanding how these molecules function in vivo is important for designing vaccines and treatments based on broadly neutralizing antibodies. For example, quantitative analysis of data on passive immunization of macaques with 2G12 and 2F5 prior to viral challenge [5] [6] [7] suggested that the administration of antibodies could decrease the numbers of cells initially infected and modulate the long-term progress of the disease by limiting the depletion of CD4+ T cells [7]. However, Trkola et al. [3] subsequently studied whether passive immunization with these antibodies reduced the viral load in humans infected with HIV-1, after cessation of antiretroviral treatment (ART). "
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    ABSTRACT: We propose a mathematical model to interpret observations concerning the behavior of broadly neutralizing antibodies for chronic HIV in vivo. The model enables us to identify a threshold antibody level that must be achieved to decrease the viral load effectively. Although this threshold has not been reached in existing passive immunization studies, it is within range of humoral immune responses, suggesting that therapeutic vaccines are feasible. In an appendix, we develop a model of passive immunization against influenza, and acute infection.
    Full-text · Article · Nov 2011 · Vaccine
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    • "If the nadir in CD4+ T cells in acute phase drops below approximately 20 cells/µL, there is no observed partial recovery, and the animals experience a continued decline in CD4+ T cell numbers and an increase in viral load [8]. In addition, the disease outcome can be modulated by early interventions that lower the acute viremia and preserve CD4+ T cells at nadir, such as early passive administration of neutralizing antibodies [10], [11], early initiation of short-term antiretroviral treatment [3] and vaccination [12], [13]. This suggests that there might exist a threshold in the severity of the acute disease, above which later virus control is impaired. "
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    ABSTRACT: Identifying early predictors of infection outcome is important for the clinical management of HIV infection, and both viral load and CD4+ T cell level have been found to be useful predictors of subsequent disease progression. Very high viral load or extensively depleted CD4+ T cells in the acute phase often result in failure of immune control, and a fast progression to AIDS. It is usually assumed that extensive loss of CD4+ T cells in the acute phase of HIV infection prevents the establishment of robust T cell help required for virus control in the chronic phase. We tested this hypothesis using viral load and CD4+ T cell number of SHIV-infected rhesus macaques. In acute infection, the lowest level of CD4+ T cells was a good predictor of later survival; animals having less than 3.3% of baseline CD4+ T cells progressed to severe disease, while animals with more than 3.3% of baseline CD4+ T cells experienced CD4+ T cell recovery. However, it is unclear if the disease progression was caused by early depletion, or was simply a result of a higher susceptibility of an animal to infection. We derived a simple relationship between the expected number of CD4+ T cells in the acute and chronic phases for a constant level of host susceptibility or resistance. We found that in most cases, the depletion of CD4+ T cells in chronic infection was consistent with the prediction from the acute CD4+ T cell loss. However, the animals with less than 3.3% of baseline CD4 T cells in the acute phase were approximately 20% more depleted late in the infection than expected based on constant level of virus control. This suggests that severe acute CD4 depletion indeed impairs the immune response.
    Full-text · Article · Feb 2011 · PLoS ONE
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    • "Passive transfer of human neutralizing antibodies can protect monkeys against intravenous or intravaginal SHIV89.6p challenge [34] by reducing the number of initially infected cells [35]. However, once HIV-1 infection is established, antibodies control HIV-1 replication only slightly [36], and escape mutants are rapidly selected [37]. "
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    ABSTRACT: Live attenuated measles vaccine (MV) could provide a safe and efficient pediatric vaccination vector to immunize children simultaneously against measles and human immunodeficiency virus type 1 (HIV-1). To evaluate the capacity of a vector derived from the certified Schwarz measles vaccine (MVSchw) to prime effective cytotoxic T cells (CTL) and broad neutralizing antibodies against HIV-1 conserved epitopes, we generated recombinant MVSchw viruses expressing HIV-1 antigens. We demonstrate that a recombinant MVSchw virus expressing an HIV-1-derived CTL polyepitope primes effective HLA-A0201-restricted CTLs against multiple conserved HIV-1 epitopes in mice susceptible to measles and humanized for the major histocompatibility complex (MHC) class-I molecule HLA-A0201. Additionally, we show that a recombinant MVSchw virus expressing an HIV-1(89.6) gp140 glycoprotein whose hyper variable V1, V2 and V3 loops were deleted (DeltaV1V2V3gp140), induces broadly neutralizing antibodies against HIV-1 primary isolates. These results show that the MVSchw pediatric vaccination vector induces efficient cellular and humoral HIV-specific immune responses.
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