Recent advances in development of avian flu and influenza diagnostics.
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Animals↗
Biomedical subjects
Aldar S Bourinbaiar
Publications and source records attributed to Aldar S Bourinbaiar.
Autoimmunity, alloimmunization and immunotherapy of AIDS.
The nature of clinical and physiological manifestations associated with HIV infection suggests that AIDS is an autoimmune disease. The conventional immunotherapeutic approaches aimed at enhancing the immune response against HIV have repeatedly failed when applied in the clinical practice. The results of several dozen therapeutic AIDS vaccine trials have consistently shown that while in vitro measured HIV-specific immune responses were evident as a result of vaccination the clinical improvement has been seldom observed. The clinical benefit, however, was invariably associated with the usage of vaccines that acted in accord with the principles of alloimmunization. The majority of these vaccines were derived from the blood of HIV carriers or a cell culture and thus they inherently contained alloantigens unrelated to HIV. The clinical experience with alloimmunization in a range of autoimmune diseases indicates that immune tolerization is an active immune process with benefits the vaccinees. The alloimmunization, which primarily induces tolerance rather than immune activation, might be a better strategy for the immunotherapy of AIDS.
Acquired Immunodeficiency Syndrome↗
Prolonged survival of end-stage AIDS patients immunized with therapeutic HIV vaccine V-1 Immunitor.
Death, rather than surrogate markers, is a single and most straightforward clinical endpoint, defining unequivocally the merit of a therapeutic intervention. As there is still neither a cure for AIDS nor a vaccine to prevent HIV infection, an AIDS diagnosis remains associated with a death sentence. V-1 Immunitor (V1) is an experimental, oral, therapeutic AIDS vaccine licensed as a dietary supplement. As part of a charity program V1 has been offered at Wat Phra Baht Nam Phu--a Buddhist hospice for end-stage AIDS patients. Out of 117 approached individuals, 53 decided to take V1 and 64 declined the treatment. Patients in both groups did not differ in age, gender, or severity of disease. All patients were in WHO terminal stage 4 at study entry and had received similar palliative care. None of the patients had received conventional antiviral drugs. At 9 weeks the last two patients in the non-V1 group died. In contrast, 56.6% (30/53) in the V1 group remained alive. Kaplan-Meier survival analysis showed that median short-term survival time for non-treated and treated patients was 4 and 10 weeks, respectively. The difference was statistically significant by Wilcoxon signed rank test (P=0.000089). Patients who remained alive were followed until the last patient died at 142 weeks. Based on the main outcome, i.e. time to death, patients on V1 had a 15.8 times longer life expectancy than the control group (P<0.000001). Observed results are encouraging and V1 needs to be tested in controlled clinical trials as a life-saving immunotherapy.
AIDS Vaccines↗
Clinical experience with therapeutic AIDS vaccines.
Recently, there has been a renewed interest in therapeutic vaccination as an adjunct or alternative to current treatment options for HIV. The first immunotherapeutic trial relevant to this topic was published in 1983. Since then, several dozen therapeutic vaccine trials have been carried out. The results have consistently shown that although in vitro-measured HIV-specific immune responses were evident as a result of vaccination, clinical improvement has been seldom observed. The instances of apparent clinical benefit however, were invariably associated with the usage of vaccines that acted in accord with the principles of allo- or autoimmunization. The majority of these vaccines were derived from the blood of HIV carriers or a cell culture and therefore inherently contained host-cell antigens unrelated to HIV. These observations raise the issue of whether this clinically successful approach has been unduly neglected. Most commercial vaccines on the market today are made the old-fashioned way, but very little support or attention has been given to the development of such vaccines for AIDS therapy. The current strategy, biased toward vaccines which have shown little evidence of clinical efficacy, is shortsighted and needs to be revised.
AIDS Vaccines↗
[AIDS vaccines and immunotherapy of infertility].
The development of prophylactic AIDS vaccines and immunotherapeutic approaches such as therapeutic AIDS vaccines would greatly benefit from acquired experience in reproductive immunology field relating to pregnancy and infertility. Certain immune and pathological aspects of HIV infection are closely related to problems faced by obstetricians, embryologists, gynecologists, and andrologists. This review attempts to bring together the recent advances in AIDS field with progress made in the physiology and pathology of reproduction in humans. The insight gained in reproductive biology research, particularly in the area of immunotherapy of recurrent spontaneous abortions, can help to develop better strategies for the treatment and prevention of HIV infection.
AIDS Vaccines↗
Phase II placebo-controlled study of V-1 Immunitor as a therapeutic modality for treatment of HIV.
BACKGROUND: V-1 Immunitor (V1) is an oral AIDS vaccine containing heat- and chemically-inactivated viral antigens derived from pooled blood of HIV-positive donors. V1 has a pending status as an investigational drug but is currently marketed as a dietary supplement. Earlier published, uncontrolled studies of V1 demonstrated body weight gain, increase in T-lymphocyte numbers, decrease in viral load, and improved survival of end-stage AIDS patients. OBJECTIVES AND STUDY DESIGN: In order to substantiate prior observations we have undertaken a placebo-controlled phase II clinical trial involving 47 antiviral therapy naive, asymptomatic individuals who had over 350 mm(3) CD4 T-cells (mean/median 538/480) at study entry. Both placebo and treatment arms were identical demographically and by every clinical parameter measured at baseline. RESULTS AND CONCLUSIONS: At the end of 6-month follow-up 29 volunteers who received V1 b.i.d. had gained on average 43 CD4 T-cells (540 versus 583). This gain was statistically significant (p=0.01) while changes in T-cell numbers in placebo group failed to reach the significance threshold (p=0.33). The clinical potential of V1 is further supported by an elevation in CD4/CD8 ratio among V1 recipients and decline in CD4/CD8 ratio in patients on placebo (0.575 versus 0.524; p=0.02). The average weight gain among patients on V1 was 1.8 kg while placebo group lost 0.5 kg. These results suggest that V1 may delay or reverse the disease progression without any concurrent toxicity and support our prior open-label studies indicating that V1 confers clinical benefit. A phase III clinical study is required to confirm these findings and to allow us to seek license for V1 as a therapeutic AIDS vaccine.
AIDS Vaccines↗
V-1 Immunitor: oral therapeutic AIDS vaccine with prophylactic potential.
V-1 Immunitor (V1) is a therapeutic vaccine comprising pooled HIV antigens formulated into an oral pill. Recent V1 studies demonstrated body weight gain, increase in CD4 and CD8 cells, decrease in viral load, and improved survival of end-stage AIDS patients. The potential of V1 as a prophylactic vaccine has been evaluated in a phase II placebo-controlled trial on 35 volunteers. Twenty HIV-negative volunteers who received V1 b.i.d. for 4 weeks had gained 28.2 and 17.5% in absolute CD4 (825 versus 1058; P=0.007) and CD8 (597 versus 702; P=0.013) cells, while lymphocytes in placebo group did not increase, suggesting that CD4 and CD8 counts may become an easily measurable immune correlate of the efficacy of AIDS vaccines. V1 does not appear to induce HIV-specific antibodies as orally administered immunogens usually produce cell-mediated but not systemic humoral response. V1 as a preventive oral vaccine targeting cellular and mucosal immunity deserves further evaluation.
AIDS Vaccines↗
Mucosal AIDS vaccines.
Debates are still being waged over what is the best strategy for developing a potent AIDS vaccine. All the obvious approaches to making AIDS vaccines have been tried in the past two decades without much success. It is clear that new thinking and a revision of prevailing dogmas needs to be in place if we really want a vaccine. Conventional envelope-based antibody-inducing vaccines do not appear to hold promise, and broadly-neutralizing antibodies are now being searched as an alternative to the failed approach with subunit vaccines. The current consensus is that cellular immune responses, especially those mediated by CD8 cytotoxic/suppressor (CTL) and CD4 helper T lymphocytes, are needed to control HIV. Vaccines capable of inducing cell-mediated responses are, therefore, considered critical for controlling the spread of HIV. DNA-based vaccines triggering CTL reaction are currently thought to be an answer, but will they fulfill the promise? In the following paragraphs, a critical assessment of the state of the art will be provided in an attempt to analyze what we know and still don't know. The focus of this review is primarily on mucosal vaccines-a relatively new area in AIDS research. The update on V-1 Immunitor, the first mucosal AIDS vaccine available commercially, is provided within this context. Some of the reviewed concepts may be disputable, but without departure from the uninspiring consensus no substantial progress in the AIDS vaccine field can be envisioned.
AIDS Vaccines↗
Low-cost anti-HIV compounds: potential application for AIDS therapy in developing countries.
A considerable progress has been made in recent years in the field of drug development against HIV. However, the current cost of AIDS drugs is the main obstacle that prevents their use in developing countries, where 95% of HIV-infected patients reside. The average yearly price of AIDS therapy and related health care of affected patients in the USA runs as high as $22,000 - an amount that corresponds to the combined income of as many as one hundred individuals in developing countries. Even in the USA, patients without medical insurance cannot afford the costly therapy. From the beginning it was clear that the most feasible and economic means of finding a solution is to identify anti-HIV drugs among already available and preferably over-the-counter pharmaceuticals, which have historically been used for unrelated clinical purposes. This review summarizes the development and discovery of affordable and potentially promising AIDS drugs. The anti-HIV activity of drugs and immunomodulating substances such as warfarin, cimetidine, levamisole, acetaminophen, gramicidin, and V-1 immunitor are described and discussed in relation to their clinical application. These compounds may be used in a cocktail drug combination.
AIDS Vaccines↗
Safety and efficacy of an oral HIV vaccine (V-1 Immunitor) in AIDS patients at various stages of the disease.
PURPOSE: To evaluate the safety and efficacy of an orally available, therapeutic HIV vaccine (V-1 Immunitor) in patients who were not treated with antiviral drugs. METHOD: All entrants who had been tested at least once at entry and at postimmunization were considered for analysis. Main endpoints were vaccine safety and differential effects on CD4 and CD8 cell counts, plasma HIV RNA levels, and body weight change. Forty patients, 21 females (52%) and 19 males (48%), aged 22-65 years (mean/median age, 35/32 years) with a mean 225/mm3 CD4 cells at baseline were retrospectively analyzed. Patients self-administered two 850-mg pills containing inactivated HIV-1 antigens b.i.d. for 27 weeks (median, 24 weeks). RESULTS: The treatment was well tolerated without significant adverse effects. The mean body weight gain was 2.2 kg (p =.0004). The mean increase in absolute CD4 and CD8 cells was 51 (18%; p =.0088) and 172 (16%; p =.0199) cells/mm3. Viral load was measured by polymerase chain reaction (PCR) in 8 individuals; although overall decrease did not reach standard cut-off statistical significance (Friedman p =.0588), the trend in reduction of viremia attributable to vaccine administration was highly significant (Spearman correlation test: r = 0.96, p =.0005). CONCLUSION: Mucosal delivery of HIV antigens provides compelling results and deserves further evaluation in placebo-controlled clinical trials.
AIDS Vaccines↗
Survival of end-stage AIDS patients receiving V-1 Immunitor.
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AIDS Vaccines↗