Showing papers on "Vaccine trial published in 2007"

A phase 1/2 comparative vaccine trial of the safety and immunogenicity of a CRF01_AE (subtype E) candidate vaccine: ALVAC-HIV (vCP1521) prime with oligomeric gp160 (92TH023/LAI-DID) or bivalent gp120 (CM235/SF2) boost.

Abstract: Background The development of an effective HIV-1 vaccine is critical to control the pandemic. A prime-boost HIV-1 vaccine trial assessing safety and immunogenicity was conducted in Thailand as part of an evaluation of candidate regimens for a phase 3 efficacy trial. Methods ALVAC-HIV (vCP1521), expressing circulating recombinant form 01_AE (CRF01_AE) gp120/subtype B LAI and subtype B Gag/Protease boosted with recombinant envelope oligomeric CRF01_AE gp160 (ogp160) or bivalent CRF01_AE/subtype B gp120 CM235/SF2, was evaluated in a phase 1/II trial of 130 HIV-negative Thai adults. Results One hundred forty volunteers were enrolled, and 130 completed all safety and immunogenicity visits. Reactogenicity was common but generally mild, and there was no significant difference in the adverse event rate between vaccine and placebo recipients (P = 0.26). There were 7 serious adverse events during the follow-up period, none of which were vaccine related. Cumulative HIV-specific, CD8-mediated, cytotoxic T-lymphocyte responses were observed in 11 (25%) of 44 subjects who received ALVAC boosted by bivalent gp120 and in 5 (11%) of 45 subjects who received ALVAC boosted by ogp160, but these differences were not statistically significant compared with those in placebo recipients (P = 0.62 and P = 0.37, respectively). HIV-specific lymphoproliferative responses were detected in 84% of subunit-boosted vaccine recipients and in 10% of placebo recipients. Neutralizing antibody responses to CRF01_AE and subtype B laboratory strains were seen in 95% of ogp160-boosted and 100% of gp120 B/E-boosted vaccinees, respectively. Conclusions These 2 different prime-boost regimens seem to be safe and displayed cell-mediated immune responses consistent with those in other trials of canarypox vectors.

Prime-Boost Vaccination Strategy in Women with High-Grade, Noncervical Anogenital Intraepithelial Neoplasia: Clinical Results from a Multicenter Phase II Trial

Abstract: The objective of this study was to determine the clinical effectiveness of a prime-boost human papillomavirus (HPV) vaccine regimen. A nonrandomized phase II prime-boost vaccine trial was conducted. Women with biopsy-proven anogenital intraepithelial neoplasia (AGIN) 3 were vaccinated with three doses of a recombinant fusion protein comprising HPV 16, E6/E7/L2 (TA-CIN) followed by one dose of a recombinant vaccinia virus encoding HPV 16 and 18 E6/E7 (TA-HPV). Clinical responses were evaluated by serial photographs, symptomatology, and biopsies before and after vaccination. Twenty-nine women were vaccinated; 27 with vulval intraepithelial neoplasia 3 and 2 with vaginal intraepithelial neoplasia grade 3. Clinical responses were seen in five women (17%), with one complete and five partial responses. Fifteen women (62%) had symptomatic improvement. No serious adverse effects were recorded. This is the first trial of a prime-boost vaccination regimen using heterologous HPV vaccines (TA-CIN followed by TA-HPV) in the management of AGIN. Since the prime-boost approach in this cohort offered no significant advantages over single TA-HPV vaccination, there are no further studies planned using this protocol. Future studies are warranted to define responders to immunotherapy.

Functional antibodies elicited by two heptavalent pneumococcal conjugate vaccines in the Finnish Otitis Media Vaccine Trial.

Abstract: In the Finnish Otitis Media Vaccine Trial, the now-licensed pneumococcal conjugate vaccine containing polysaccharides conjugated to protein CRM197 (PncCRM) and the experimental pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PncOMPC), showed similar efficacy profiles against acute otitis media despite different antibody concentrations in sera. We now report the opsonophagocytic activities (OPA) in these sera. OPA, antibody concentration, and avidity for serotypes 6B, 19F, and 23F were determined in sera of infants who received either pneumococcal conjugate (PCV) or control vaccine at 2, 4, and 6 months of age and either the homologous or pneumococcal polysaccharide vaccine at 12 months of age. OPA varied by vaccine and serotype. The majority of PCV recipients had positive OPA after the fourth dose, while OPA was undetectable in the control group. Coinciding with the efficacy data, the concentration of antibodies required for 50% killing was low for 6B and high for 19F for both PCVs. Contradictory to the efficacy data, PncOMPC induced lower functional capacity to 23F than PncCRM. OPA correlated with antibody concentration, while avidity and functional capacity of antibodies showed no correlation. The OPA data provide valuable additional information for serotype-specific differences in protection and when evaluating serotype-specific immunogenicity and should thus be considered when defining serological correlates of protection.

Improving comprehension for HIV vaccine trial information among adolescents at risk of HIV.

Abstract: A simplified version of the HIVNET prototype HIV vaccine process was developed for adolescents at risk of HIV by: (1) reducing reading level; (2) reorganizing; (3) adding illustrations; and (4) obtaining focus group feedback. Then adolescents (N = 187) in three cities were randomly assigned to the standard or simplified version. Adolescents receiving the simplified version had significantly higher comprehension scores (80% correct vs. 72% correct), with 37% of items significantly more likely to be answered correctly. They were also significantly more likely to recall study benefits and procedures. Overall, adolescents were less willing to participate in a potential HIV vaccine trial after presentation than prior to presentation. The present study indicates that it would be feasible for adolescents to participate in a vaccine trial, as simplification of vaccine information, combined with illustrations to depict key concepts, resulted in improved scores for adolescents on the comprehension and reca...

Lung cancer vaccines.

Abstract: Cytotoxic chemotherapy is associated with modest survival advantage as initial treatment of advanced lung cancer. However, toxicity and minimal benefit to use second line treatment justifies exploration of alternative approaches. Recent understanding of mechanisms by which tumor antigen recognition can be enhanced has justified development of a recent flurry of vaccine trials in lung cancer. Preliminary results suggest a remarkably high safety profile and significant activity with respect to improvement in time to progression and survival in comparison to historical controls or lower dose treated cohorts, particularly in non small cell lung cancer. This review summarizes current results of vaccine trial development in non small cell and small cell lung cancer.

WITHDRAWN: Vaccines for preventing malaria.

Abstract: Background Four types of malaria vaccine, SPf66 and MSP/RESA vaccines (against the asexual stages of the Plasmodium parasite) and CS-NANP and RTS,S vaccines (against the sporozoite stages), have been tested in randomized controlled trials in endemic areas. Objectives To assess malaria vaccines against Plasmodium falciparum, P. vivax, P. malariae and P ovale in preventing infection, disease and death. Search strategy We searched the Cochrane Infectious Diseases Group Specialized Register (April 2004), CENTRAL (The Cochrane Library Issue 2, 2004), MEDLINE (1966 to April 2004), EMBASE (1980 to April 2004), Science Citation Index (1981 to April 2004), and reference lists of articles. We also contacted organizations and researchers in the field. Selection criteria Randomized controlled trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale with placebo or routine antimalarial control measures in people of any age receiving a challenge malaria infection. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. Main results Eighteen efficacy trials involving 10,971 participants were included. There were ten trials of SPf66 vaccine, four trials of CS-NANP vaccines, two trials of RTS,S vaccine, and two of MSP/RESA vaccine. Results with SPf66 in reducing new malaria infections (P. falciparum) were heterogeneous: it was not effective in four African trials (Peto odds ratio (OR) 0.96, 95% confidence interval (CI) 0.81 to 1.14), but in five trials outside Africa the number of first attacks was reduced (Peto OR 0.77, 95% CI 0.67 to 0.88). Trials to date have not indicated any serious adverse events with SPf66 vaccine. In three trials of CS-NANP vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (Peto OR 1.12, 95% CI 0.64 to 1.93). In a small trial in non-immune adults in the USA, RTS,S gave strong protection against experimental infection with P. falciparum. In a trial in an endemic area of the Gambia in semi-immune people, there was a reduction in clinical malaria episodes in the second year of follow up, corresponding to a vaccine efficacy of 66% (CI 14% to 85%). In a trial in Papua New Guinea, MSP/RESA had no protective effect against episodes of clinical malaria. There was evidence of an effect on parasite density, but this differed according to whether the participants had been pretreated with sulfadoxine/pyrimethamine or not. The prevalence of infections with the parasite subtype of MSP2 in the vaccine was reduced compared with the other subtype (Peto OR 0.35, CI 0.23 to 0.53). Authors' conclusions There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America or with new formulations of SPf66 may be justified. There was not enough evidence to evaluate the use of CS-NANP vaccines. The RTS,S vaccine showed promising result, as did the MSP/RESA vaccine, but it should include the other main allelic form of MSP2. The MSP/RESA trial demonstrated that chemotherapy during a vaccine trial may reduce vaccine efficacy, and trials should consider very carefully whether this practice is justified.

Economic evaluations of human papillomavirus vaccines

Abstract: Vaccines to prevent infection with the human papillomavirus (HPV) have recently been approved for use in preventing cervical precancer and cancer. This paper reviews the HPV vaccine effectiveness and cost–effectiveness studies published to date. In order to fully appreciate the strengths and limitations of the different studies, a short background is provided on the natural history of HPV and cervical cancer, current prevention strategies and HPV vaccine trial results to date. Each study is then summarized in terms of model structure, parameter estimates for the natural history of HPV and cervical cancer, assumptions regarding screening and vaccination, and key findings. The review concludes with recommendations for additional research and a five-year perspective.

Social harms in injecting drug users participating in the first phase III HIV vaccine trial in Thailand.

Abstract: The objective was to study related social harms due to identification with a group of participants in an HIV-1 vaccine trial who are potentially high risk for HIV/AIDS. Two thousand five hundred forty six injecting drug users (IDU) were enrolled in a 36-month vaccine trial. Volunteers received education and risk reduction counseling at every six-month study visit. Social harms were not actively solicited but volunteers were encouraged to report any during the process of counseling at every six-month visit. If a social harm was reported a questionnaire was administered and the harm was tracked. If necessary clinic staff assisted in resolving the social harm. Thirty-nine social harms were reported by 37 participants; 33 (84.6%) were disturbances in personal relationships three (7.7%) in employment one (2.6%) was medically related one (2.6%) was related to admission in the military and one (2.6%) was related with misbelieve about the vaccine. The most common reason for disturbances in personal relationships was suspicion of HIV infection (n = 20). The impact of these harms on quality of life was characterized as minimal by 31 (79.5%) participants as moderate by seven (17.9%) and as major by one (2.6%). All social harms were documented to be resolved by the end of the study. A few participants reported study-related social harms during the course of the trial. Most harm had minimal impact and all could be resolved by the end of the present study. (authors)

Adolescent Participation in HIV Vaccine Trials: Cognitive Developmental Considerations

Abstract: Adolescents form an important target group for HIV vaccine trials for a number of reasons. These include the high HIV prevalence and incidence rates amongst adolescents, early sexual debut,multiple sexual partners, and other high-risk sexual behaviours. It has therefore been argued that the focus of HIV vaccination attempts should be on early adolescents younger than 15 years of age. Indeed, vaccination of adolescents prior to their sexual debut has been argued to have the potential to be one of the most effective ways to curb the HIV pandemic. While the biological and epidemiological arguments for vaccination of adolescents have been elucidated, this article offers some insight into the cognitive aspects of decision making in adolescence that may inform strategies vaccine trial sites might employ when dealing with adolescent participants. After a brief overview of the educational, biological, and relationship changes that occur during adolescence, this article explores some of the more pertinent cognitive changes that occur during adolescence.More specifically, this article explores the cognitive changes during adolescence that affect decision making, such as differences between younger and older adolescents in (a) choice, (b) comprehension, (c) creativity, (d) compromise, (e) consequentiality, (f) correctness, (g) credibility, (h) consistency, and (i) commitment. Research findings relating to the above changes are discussed, creating an argument for the exclusion of early adolescents in vaccine trials and the concomitant active engagement with middle adolescents.

Vaccines for Cholera Control: Does Herd Immunity Play a Role?

Abstract: The author discusses a new study that mathematically simulated different vaccine coverage levels in the Matlab region of Bangladesh using a historic vaccine trial dataset.

A randomized phase II p53 vaccine trial comparing subcutaneous direct administration with intravenous peptide-pulsed dendritic cells in high risk ovarian cancer patients

Abstract: 3011 Background: 50% of ovarian cancers carry a p53 mutation, most of which can lead to overexpression of the protein, providing a unique target for vaccine therapy. Preclinical data shows cytotoxi...

Prevention strategies: herpes zoster, post-herpetic neuralgia and immunogenicity.

Abstract: Herpes zoster is a common condition that can have a significant impact on quality of life among older adults. A significant proportion of older subjects with herpes zoster develop post-herpetic neuralgia (PHN), a chronic condition that is difficult to treat. The Shingles Prevention Study was a large-scale clinical trial to determine the efficacy of a live, attenuated varicella zoster virus (VZV) vaccine ('zoster vaccine') for preventing or attenuating herpes zoster in subjects aged > or =60 years. A total of 38 546 subjects were given either zoster vaccine or placebo. The burden of illness (pain severity-by-duration), incidence of herpes zoster, and PHN decreased by 61.1%, 51.3% and 66.5% (all P<0.001), respectively, following vaccination. Vaccine efficacy was maintained for a 4-year follow-up period. A sub-study of the vaccine trial evaluated VZV-specific immunity in approximately 1200 vaccine or placebo recipients prior to vaccination, at 3 months and annually for 3 years. VZV-specific cell-mediated immunity (CMI) was boosted significantly by the zoster vaccine. This boost remained substantially intact for the 3 years of follow-up. It is likely that the vaccine-induced boost in VZV-specific CMI reversed the natural decline in these responses that occurs as part of the ageing process, thereby protecting vaccine recipients against herpes zoster and its complications.

Faulty government condoms threaten South Africa's AIDS programme.

Abstract: The recall of defective free condoms issued by the South African government, along with last month's sudden suspension of a major vaccine trial, could have a disastrous effect on the fight against AIDS in the country, campaigners fear. In August 20 million defective, locally manufactured condoms were recalled from circulation in South Africa, which has the world's highest burden of HIV and AIDS. The recall resulted in widespread panic and a political scandal, and then last month a second batch of millions of free condoms was also withdrawn. Warren Parker, director of the Centre for AIDS Development, Research and Evaluation, said, “Having a second condom recall severely …

Mucosal innate immune factors in secretions from high-risk individuals immunized with a bivalent gp120 vaccine.

Abstract: This study examined the effect of an HIV vaccine on mucosal innate factor expression. Serum, gingival fluid, and genital mucosal secretions were collected from high-risk women and men enrolled in an HIV-1 efficacy vaccine trial and from low-risk women and men. Samples were tested by standard ELISA for lactoferrin, myeloid-related protein-8/14, and secretory leukocyte protease inhibitor. No consistent significant changes in innate factor levels were found in serum or secretions from vaccinees compared to placebo recipients or from high-risk compared to low-risk individuals. Because of the importance of innate immunity in host defense, evaluation of the mucosal innate immune system should be included in future HIV prevention trials.

HIV/AIDS Vaccines: How long must humanity wait?

Abstract: OVER FORTY MILLION PEOPLE ARE INFECTED with the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS), and more than 95% of these infected individuals are in the developing countries. The prevalence levels for this virus will continue to rise globally. The HIV/AIDS pandemic is the most devastating global public health crisis since the great plagues of the middle-ages with approximately fifteen thousand new HIV infections and ten thousand deaths due to AIDS every day and approximately 3.1 million total deaths due to AIDS.1 Historically, vaccines have proven to be the most effective weapon in our fight against infectious diseases such as small pox, polio, measles and yellow fever. HIV vaccines are our best hope to end the HIV pandemic. Although successful vaccines have been developed for the common childhood diseases, the development of a vaccine against the AIDS virus is a much greater challenge. The best way to stop the spread of the disease and the suffering of AIDS patients is by the development of successful vaccines to prevent infection with HIV and delay or stop progression to AIDS. It is now two decades and a half since HIV was first discovered and researchers have spent millions of Riyals (Omani currency; 1 Riyal = 2.6 US$) looking for possible candidates as vaccines, but what is the outcome of this research? It seems the discovery of a licensed and globally accessible HIV/AIDS vaccine is still years away, the question that arises is: how soon are we going to see a successful HIV/AIDS vaccine? More realistically, how long are we going to wait for such a vaccine? In this article, I will very briefly touch on the scientific hurdles that have impeded the search for an effective AIDS vaccine and discuss novel research approaches to accelerate its progress. Despite important progression in the understanding of HIV pathogenesis2 and HIV/AIDS virus compared to any other viral disease, why are we still not able to produce an effective or even partially effective HIV/AIDS vaccine? The answer to this question lies in understanding how the virus evades the immune system. First, HIV disables the very cells that are responsible for fighting it. Second, HIV is able to integrate its viral genome into the chromosome of the infected cells and therefore hide from recognition by the immune response for many years. Third, HIV is able to conceal the protein components that can induce protective immune responses and therefore presents itself to the body in a way that makes it difficult for the immune system to respond effectively. Fourth, HIV is genetically diverse and rapidly changing, particularly its outer envelope, and this allows the virus to evade most of the natural and protective immune mechanisms that the immune system is able to make. As soon as HIV infection becomes established, HIV continues to mutate genetically and many variants may arise within an infected person. Therefore, investigators need to know the significance of strain variation within the individuals and among the populations when developing an effective HIV/AIDS vaccine. The most logical approach for designing an effective HIV/AIDS vaccine is to identify which immune responses are most protective against this virus infection and to construct a vaccine that is able to stimulate these protective responses. Of the two main types of immune responses, the humoral immune response mainly uses antibodies to protect against a cell-free virus, whereas the cell mediated immune response is essential for body defense when the virus is hidden inside the cells. Although earlier vaccine research focused primarily on vaccines that elicited antibodies, it is now generally believed that both arms of the immune response are required in order to control and prevent HIV infection. Moreover, much attention has recently been directed towards vaccines that induce good innate (natural) immune responses particularly dendritic cells and toll-like receptors which play an important role in inducing and modulating the adoptive immune responses.3 The most practical goal for an HIV vaccine is to prevent HIV transmission rather than preventing infection with the virus. Experts believe a vaccine is the only way to eradicate HIV/AIDS because the most common modes of transmission, sexual contact, injection drug use and mother-to-child transmission at childbirth or breast-feeding are impossible to eliminate completely. The main characteristics of a desirable HIV vaccine are: safety, simple administration as well as affordable cost, long lasting immunity and effective against all HIV subtypes. To develop such an HIV/AIDS vaccine there is a need for team work in fundamental basic research; preclinical screening for active candidates and appropriate animal model followed by product development, manufacturing, and clinical research.3 Currently, there are more promising vaccine candidates being tested than ever before. Vaccine candidates are being constructed based on isolates from different regions of the world, and several research groups are testing a cocktail or a mixture of different viral components from different isolates of HIV. In addition, to optimize the immune responses, new vaccine strategies are being tested [Table 1]. The most current HIV vaccine candidates focus on producing cytotoxic CD4+ T cells, which attack HIVinfected cells in the body; such vaccines might not prevent an HIV-negative person from contracting the virus, but would delay HIV from progressing to AIDS and prevent transmission to others. Another challenge in vaccine research is that HIV strains vary among people and regions. Vaccine trial participants are chosen based on health standards for industrialized nations and many people in developing countries are not healthy enough to participate in such trials.4 Vaccineinduced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines; however, for highly variable viruses such as HIV-1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV-1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and virus entry. HIV-1 has evolved many mechanisms on the surface of envelope glycoproteins to evade antibody-mediated neutralization, including the masking of conserved regions by glycan, quaternary protein interactions and the presence of immunodominant variable elements. The primary challenge in the development of an HIV-1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers.5 Individuals who are infected with HIV but remain healthy and keep viral replication in check may offer some hope for guiding the design of an effective HIV vaccine.6 Some of these long-term survivors make a very small amount of antibody, which, when isolated, can neutralize HIV from patient isolates. Further, those antibodies can neutralize viruses from many different patient isolates, which is necessary for an AIDS vaccine that will be effective against a broad spectrum of HIV strains. Unfortunately, even these antibodies may not be the whole answer. Tests of cells in culture indicate that the antibodies must be present at surprisingly high concentrations to block HIV entry into cells effectively. Many researchers continue to look into developing a live, attenuated HIV vaccine despite safety concerns. Because such a vaccine would closely mimic active HIV, it should theoretically be effective at inducing cellular immunity, antibody-based immunity and perhaps- other unknown modes of protection. By systematically deleting genes critical for HIV replication, scientists hope to develop a variant of the virus that can elicit a strong immune response without giving rise to AIDS.4 It also is hoped that vaccines may give the body an immunological ‘head start’ by priming the immune system to attack HIV as soon as it appears, rather than taking time to initiate a defense from scratch. As the pathogenesis of HIV infection has become better understood, investigators have realized that if the virus can be kept at low concentrations in the blood, an infected person may never progress to AIDS.7 This insight is encouraging because it suggests that even a partially effective vaccine could be valuable in limiting the amount of virus in patients, thus potentially reducing virus infectiousness and the AIDS symptoms. The multitude of scientists searching for successful AIDS vaccines will require appropriate funding and ample time. Funding is now improving, but because of the above difficulties we may not see a vaccine in near future.8 Governments need to cooperate to break barriers, reduce the stigma associated with HIV/AIDS, encourage HIV testing, provide support for people with HIV/AIDS and allocate appropriate funding to institutes that work for the development of HIV/AIDS vaccines. The development of appropriate antiviral therapy and reconstructing the damaged immune system are two approaches, both of which require significant financial support. For developing countries, educating the public on preventative measures is the first step in preventing and reducing the spread of HIV/AIDS. Treating those infected with HIV or who have AIDS is also, of course, critical, but the real hope for the future lies in developing a successful vaccine.