T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients?An extended open trial

Abulafia-Lapid, Rivka; Mayan, Shlomo; Bentwich, Zvi; Keren-Zur, Yael; Avbramovitz, Yulia; Cohen, Irun R.; Atlan, Henri

doi:10.1016/j.vaccine.2005.01.054

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…A further in vivo proof of principle of the importance of this mechanism was provided by Abulafia-Laid et al . [16], who showed the efficacy of T-cell vaccination against anti-CD4 autoimmunity in a small sample of HIV-infected patients. Intracellular interactions of newly synthesized CD4 molecules with various HIV proteins may be the basis for the generation of various self-epitopes, which in the absence of HIV are ignored due to tolerance mechanisms.…”

Section: Mechanisms For Breaking Of Tolerance Following Hiv-1 Expomentioning

confidence: 99%

Protective versus pathogenic anti-CD4 immunity: insights from the study of natural resistance to HIV infection

et al. 2009

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HIV-1 exposure causes several dramatic unbalances in the immune system homeostasis. Here, we will focus on the paradox whereby CD4 specific autoimmune responses, which are expected to contribute to the catastrophic loss of most part of the T helper lymphocyte subset in infected patients, may display the characteristics of an unconventional protective immunity in individuals naturally resistant to HIV-1 infection. Reference to differences in fine epitope mapping of these two oppositely polarized outcomes will be presented, with particular reference to partially or totally CD4-gp120 complex-specific antibodies. The fine tuning of the anti-self immune response to the HIV-1 receptor may determine whether viral exposure will result in infection or, alternatively, protective immunity.Along this line, an efficacious anti-HIV strategy can rely on the active (i.e., through immunization) or passive targeting of cryptic epitopes of the CD4-gp120 complex, including those harboured within the CD4 molecule. Such epitopes are expected to be safe from genetic drift and thus allow for broad spectrum of efficacy. Moreover, since these epitopes are not routinely exposed in uninfected individuals, they are expected to become targets of neutralizing antibodies or other specifically designed molecules only after viral exposure, with a predictable low impact in terms of potentially harmful anti-CD4 self-reactivity.The experimentum naturae of naturally resistant individuals indicates a strategy to design innovative strategies to neutralize HIV-1 by acting on the sharp edge between harmful and protective self-reactivity.

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Section: Mechanisms For Breaking Of Tolerance Following Hiv-1 Expomentioning

confidence: 99%

Protective versus pathogenic anti-CD4 immunity: insights from the study of natural resistance to HIV infection

et al. 2009

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“…While the level of viremia did not seem to change the authors were able to observe significant clinical improvements not seen in control patients [72]. The follow-up study revealed that 7/8 subtype B and 2/4 subtype C patients responded with a persistent increase in their blood CD4 T-cell levels [73]. Remarkably, as opposed to above vaccines, the TCV preparation did not contain HIV.…”

Section: Peripheral Blood-derived Inactivated Vaccinesmentioning

confidence: 89%

“…Rivka Abulafia-Lapid and her colleagues from Israel have chosen an approach that is quite similar to that of Zagury and Abalaka [72,73]. Similarly to Ngu they argued that AIDS is an autoimmune disease characterized by selfdirected destruction of helper CD4 lymphocytes and what they aimed to achieve was to induce immune tolerance [74].…”

Section: Peripheral Blood-derived Inactivated Vaccinesmentioning

confidence: 99%

Therapeutic AIDS Vaccines

Bourinbaiar¹,

Root‐Bernstein²,

Abulafia-Lapid³

et al. 2006

CPD

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Therapeutic HIV vaccines represent promising strategy as an adjunct or alternative to current antiretroviral treatment options for HIV. Unlike prophylactic AIDS vaccines designed to prevent HIV infection, therapeutic vaccines are given to already infected individuals to help fight the disease by modulating their immune response. The first immunotherapeutic trial in AIDS patients was conducted in 1983. Since then several dozen conventional therapeutic vaccine trials have been carried out. Unfortunately, the results have consistently shown that while HIV-specific immune responses were evident as a result of vaccination, the clinical improvement has been seldom observed. The instances of the apparent clinical benefit were invariably associated with unconventional vaccines that acted in accord with the principles of alloimmunization and/or autologous vaccination. All such vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained allo- or self-antigens unrelated to HIV. This intriguing observation raises the issue whether this clinically successful approach has been unduly neglected. The current strategy biased toward vaccines, which have shown little evidence of clinical efficacy, needs to be diversified and supplemented with research on alternative vaccine approaches geared toward immune tolerance induction.

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“…The autologous T-cell vaccination developed by Abulafia-Lapid et al has shown encouraging results with over 50% (median of 70%) increase in CD4 cell counts. Their vaccine consists of in vitro propagated, glutaraldehyde-inactivated, autologous T cells which are injected back to HIV-positive donors [ 44 ]. Remune is another vaccine in this category; however, due to the purification process of virus particles from the supernatant of cell culture, it may not possess sufficient quantity of alloantigens, which may explain persistent incertitude in clinical effect [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Serodeconversion of HIV Antibody‐Positive AIDS Patients Following Treatment with V‐1 Immunitor

Metadilogkul

Jirathitikal²,

Bourinbaiar³

2008

BioMed Research International

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It is extremely rare when HIV seropositive adult patients experience spontaneous loss of antibodies, that is, seroreversion. The disappearance of HIV antibodies was occasionally attributed to iatrogenic intervention—serodeconversion. Such interventions include: HAART; oral interferon; Chinese herbal remedies; and therapeutic AIDS vaccines derived from pooled blood. Oral therapeutic, alloimmune AIDS vaccine, V-1 Immunitor (V1), was administered to 60000 HIV-positive Thai patients. The administration of V1 resulted in serodeconversion among 23 individuals. The patient group consisted of 9 females (39%) and 14 males (61%) including two 2-year-old boys. The age range was 2–58 years with mean/median 29/29.3 years. Patients were tested seropositive for HIV at least once before being enrolled on V1. The duration of treatment until discovery of seronegative status ranged between 2 weeks and 15 months with average/median 7.2/8 months. Time to seronegativity was correlated with baseline disease stage (R = 0.62; P = .002). The seronegative status was positively associated with V1-induced undetectable or low viral load (R = 0.65; P = .0008). The odds ratio analysis comparing the outcome of our study with published surveys of diagnostic accuracy of laboratory tests suggested that the probability of HIV antibody testing error was remote (P < .000001). The possible causes responsible for this unusual phenomenon are discussed.

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T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients?An extended open trial

Cited by 6 publications

References 9 publications

Protective versus pathogenic anti-CD4 immunity: insights from the study of natural resistance to HIV infection

Protective versus pathogenic anti-CD4 immunity: insights from the study of natural resistance to HIV infection

Therapeutic AIDS Vaccines

Serodeconversion of HIV Antibody‐Positive AIDS Patients Following Treatment with V‐1 Immunitor

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