Showing papers on "Vaccine trial published in 1998"
TL;DR: While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.
Abstract: Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum - infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.
245 citations
TL;DR: A single dose of ALM + BCG was safe and more immunogenic than BCG alone, as measured by leishmanin skin test, and the preferential protective effect in boys may have resulted from a greater booster effect produced by repeated exposure to infected sandflies.
245 citations
TL;DR: The safety and immunogenicity of an orally administered live human rotavirus vaccine candidate (89-12), attenuated by 33 passages in monkey kidney cells, were evaluated in placebo-controlled trials in adults, children and infants and indicated that the vaccine was safe.
177 citations
TL;DR: It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials, and a variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for participation.
Abstract: Objective: To determine the willingness of populations at high risk of HIV-1 infection to participate in HIV vaccine efficacy trials, determine factors influencing decision-making, and evaluate knowledge levels of vaccine trial concepts. Design: Cross-sectional study. Methods: HlV-1-negative homosexual men, male and female injecting drug users and non-injecting women at heterosexual risk were recruited in eight cities in the United States (n = 4892). Results: A substantial proportion of the study population (77%) would definitely (27%) or probably (50%) be willing to participate in a randomized vaccine efficacy trial. Increased willingness was associated with high-risk behaviors, lower education level, being uninsured or covered by public insurance, and not having been in a previous vaccine preparedness study. Altruism and a desire for protection from the vaccine were major motivators for participation. Major concerns included positive HIV-1 antibody test due to vaccine, safety of the vaccine, and possible problems with insurance or foreign travel. Baseline knowledge of vaccine trial concepts was low. Conclusions: It is likely that high-risk volunteers will be willing to enroll in HIV vaccine efficacy trials. A variety of participant and community educational strategies are needed to address participant concerns, and to ensure understanding of key concepts prior to giving consent for concepts prior to giving consent for participation.
143 citations
Journal Article•
TL;DR: Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.
Abstract: Background Influenza vaccine is recommended for heart transplant recipients, but its administration is often deferred because of anecdotal reports of rejection associated with the vaccine. We evaluated the safety of influenza vaccine in a group of stable heart transplant recipients over a 2-year period. Methods During the 1993 to 1994 influenza season, stable heart transplant recipients who had undergone transplantation a minimum of 1 year before study entry were randomized to vaccination with a single dose of influenza vaccine versus no vaccination. Routine endomyocardial biopsies and postvaccination influenza serologic studies were performed between 2 and 6 weeks after enrollment/immunization. During the 1994 to 1995 season, patients were given 2 doses of influenza vaccine, separated by 3 weeks; endomyocardial biopsies and serologic studies were performed between 2 and 6 weeks after the second immunization or enrollment (if control subject). Biopsy results were evaluated with respect to vaccine response, immunosuppressive regimens, and patient demographics. Results Eighteen patients were enrolled in the single vaccine trial and 10 in the booster vaccine trial. Four of 14 vaccine recipients had biopsy specimens consistent with International Society for Heart and Lung Transplantation grades 2 to 3A as compared with 1 of 14 control subjects (grade 2) (p = .326). All episodes of rejection in the vaccine recipients were asymptomatic and responded to a single course of treatment. Rejection was unrelated to the time from transplantation, doses of immunosuppression, age, or number of doses of or response to vaccine. Conclusions Influenza vaccine can be safely administered to most heart transplant recipients but may be associated with low-level histologic rejection.
71 citations
TL;DR: A vaccination strategy that is a trade-off between optimal estimation of vaccine efficacy for susceptibility and of vaccine effectiveness for infectiousness is proposed and it is shown that the optimal choice depends on the anticipated efficacy of the vaccine as well as the basic reproduction number of the underlying infectious disease process.
Abstract: Vaccination can have important indirect effects on the spread of an infectious agent by reducing the level of infectiousness of vaccinees who become infected. To estimate the effect of vaccination on infectiousness, one typically requires data on the contacts between susceptible and infected vaccinated and unvaccinated people. As an alternative, we propose a trial design that involves multiple independent and interchangeable populations. By varying the fraction of susceptible people vaccinated across populations, we obtain an estimate of the reduction infectiousness that depends only on incidence data from the vaccine and control groups of the multiple populations. One can also obtain from these data an estimate of the reduction of susceptibility to infection. We propose a vaccination strategy that is a trade-off between optimal estimation of vaccine efficacy for susceptibility and of vaccine efficacy for infectiousness. We show that the optimal choice depends on the anticipated efficacy of the vaccine as well as the basic reproduction number of the underlying infectious disease process. Smaller vaccination fractions appear desirable when vaccine efficacy is likely high and the basic reproduction number is not large. This strategy avoids the potential for too few infections to occur to estimate vaccine efficacy parameters reliably.
61 citations
TL;DR: The authors use the nonparametric method to reanalyze data from a vaccine trial of two cholera vaccines in rural Bangladesh and reveal the differential protection and waning effects for the vaccines as a function of biotype and age.
Abstract: The authors present a nonparametric method for estimating vaccine efficacy as a smooth function of time from vaccine trials. Use of the method requires a minimum of assumptions. Estimation is based on the smoothed case hazard rate ratio comparing the vaccinated with the unvaccinated. The estimation procedure allows investigators to assess time-varying changes in vaccine-induced protection, such as those produced by waning and boosting. The authors use the method to reanalyze data from a vaccine trial of two cholera vaccines in rural Bangladesh. This analysis reveals the differential protection and waning effects for the vaccines as a function of biotype and age.
59 citations
TL;DR: Observations demonstrate a previously unrecognized complexity of rgp90 vaccine efficacy that has important implications for AIDS vaccine development.
48 citations
TL;DR: In this vaccine trial, few serious social harms were reported and those who conduct HIV tests for insurance, employment, health care, or other reasons should be made aware that HIV vaccines can cause false-positive HIV test results.
Abstract: CONTEXT Preventive HIV vaccines can temporarily cause uninfected individuals to have positive results on HIV testing. As preparations are underway to mount larger efficacy trials, the social risks of trial participation should be studied. OBJECTIVE To describe frequency of HIV testing and discrimination among participants in a preventive phase II HIV vaccine trial. PARTICIPANTS 266 vaccine trial volunteers were eligible; 247 participated in a confidential survey. RESULTS 63 volunteers (26% of respondents) reported 185 HIV tests during the prior 12 to 24 months; most tests were for other research studies, health care, insurance, incarceration, or employment. Only 5 volunteers reported having positive HIV test results. Volunteers reported 99 adverse social incidents or problems, 53 of which were related to the trial. The most common type of event occurred when volunteers disclosed their trial participation and were mistakenly presumed to be infected with HIV. Few reported difficulty obtaining insurance, job loss, and inadvertent disclosure of their participation in the trial. CONCLUSION In this vaccine trial, few serious social harms were reported. Those who conduct HIV tests for insurance, employment, health care, or other reasons should be made aware that HIV vaccines can cause false-positive HIV test results. Those planning future trials must continue to provide needed support to volunteers. Social harms should be monitored with the same vigilance accorded to physical harms.
48 citations
TL;DR: The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic.
Abstract: Data from recruitment and screening for a phase I/II preventive HIV-1 vaccine trial in Thailand were evaluated with respect to correlates of participation at each phase. Correlates included demographic variables, motivation for interest in the trial, and factors related to communication and contact. Participants were recruited at two sites through varied methods. The majority of prescreenees reported altruistic motives for interest in the trial and blood donors emerged as a group that may have been particularly altruistic. Findings indicated site differences in attrition during recruitment and screening, but not in enrollment into the vaccine trial. Blood donation and willingness to be contacted by phone at home were significantly related to making and keeping screening appointments.
45 citations
TL;DR: A recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden ofsevere pneumonia.
Abstract: The true burden of disease caused by Haemophilus influenzae type b (Hib) remains a mystery in many parts of the developing world. The most frequent manifestations of Hib disease are pneumonia and meningitis. In developing countries where it has been studied, Hib has proved to be a major cause of infant meningitis, generally occurring with greater frequency, in younger infants and with a worse outcome than in industrialized countries in the prevaccine era. The burden of Hib pneumonia is more difficult to define. Studies from developing countries of pneumonia etiology suggested that Hib was responsible for 5 to 10 of episodes of severe pneumonia. A Gambian study found Hib to be responsible for 7% of cases. However, a recently published trial of a Hib conjugate vaccine in Gambian infants showed that the vaccine prevented 21% of episodes of severe pneumonia in vaccine recipients, suggesting that this is the true contribution of Hib to the burden of severe pneumonia. The same trial demonstrated a mild herd effect, so this figure may be an underestimate. The biases that lead to the underestimation of the contribution of Hib to the pneumonia burden also apply to estimates of the proportion of severe pneumonia caused by Streptococcus pneumoniae. Vaccine trials may reveal the true burden of that pathogen also.
TL;DR: In this paper, the authors evaluated the willingness of clients at a large urban sexually transmitted diseases (STD) clinic in the southeastern United States to participate in future trials of preventive vaccines for HIV type 1 (HIV-1).
01 Oct 1998
TL;DR: The simulation analysis indicates that the RPT design has substantially greater statistical power for identifying vaccines which, in spite of exhibiting poor protection against infection, are nonetheless capable of halting the HIV epidemic by substantially reducing the infectiousness of vaccinated individuals who become infected.
Abstract: Many HIV vaccine trials have been proposed to evaluate susceptibility of individuals. However, vac cines may also affect an epidemic's course at the population level by altering the infectiousness of vaccinated individuals who become infected. A vac cine trial design that does not estimate both suscep tibility and infectiousness might reject a proposed vaccine that is capable of halting the HIV epidemic. We describe a vaccine trial design called the Retro spective Partner Trial (RPT), which can quantify vaccine effects on both susceptibility and infectious ness. We describe HIVSIM, a simulation environ ment that generates simulated populations and al lows for empirical evaluation of the statistical power of the RPT. HIVSIM explicitly models a number of factors which influence transmission and preva lence, and which have proven difficult to model us ing standard models. These factors include the infec tion stage of infected individuals, partnership selec tion, the duration of partnerships and concurrence, ...
TL;DR: An Hib PCR assay on blood culture supernatants proved to be sensitive and specific for the diagnosis of Hib disease in children, suggesting that most of these children had been infected with Hib.
Abstract: Background. Determination of the etiology of pneumonia in young children is difficult because blood culture, the usual method of diagnosis, is positive in only a small proportion of cases. For this reason vaccine trials that include bacterial pneumonia as an endpoint must be large. Objectives. To determine whether a diagnostic test based on a polymerase chain reaction could be used as an alternative to conventional blood culture for diagnosis of invasive Haemophilus influenzae type b (Hib) infections in young children investigated during the course of a large vaccine trial. Methods. DNA was extracted from blood culture supernatants and probed for the presence of Hib DNA with a PCR assay with primers derived from the cap gene locus of Hib. Results of the PCR assay were compared with those obtained by conventional culture techniques. Results. Blood cultures were obtained from 1544 children with suspected pneumonia, meningitis or septicemia and from 31 healthy control children who were contacts of cases. Blood culture supernatants were tested for Hib DNA in the PCR test. The sensitivity and specificity of a positive PCR test in blood culture supernatant as against culture of Hib from any normally sterile site were 100 and 99%, respectively. Eleven children had positive Hib PCR tests on blood culture supernatants but were negative by culture. In one of these cases Hib was isolated from a lung aspirate and in two other patients H. influenzae strains other than Hib were obtained from the cerebrospinal fluid. Eight of these 11 children were in the control group. When the results of the PCR assay were used to determine vaccine efficacy, a value of 86% was obtained compared with a figure of 95% obtained when conventional culture techniques were used. Conclusions. An Hib PCR assay on blood culture supernatants proved to be sensitive and specific for the diagnosis of Hib disease in children. The distribution of PCR-positive, culture-negative cases between Hib-vaccinated and control groups paralleled that of culture-positive cases, suggesting that most of these children had been infected with Hib. A trial of a highly efficacious vaccine provides a novel way for evaluating new diagnostic tests for which there is no standard diagnostic test of 100% reliability.
TL;DR: Data support the theory that IE180 may indeed play a role in the overall protective immunity against PrV, as an enhancement of immune responses and a twofold increase in the level of protection were observed in mice that received a second vaccine booster by gene gun 8 months after the first vaccination.
Abstract: An earlier study in our laboratory provided evidence that pseudorabies virus (PrV) immediate early protein (IE180) may contribute to the overall immune response against PrV. To examine the response by IE180 more closely, we initiated a vaccine trial in mice with a vector DNA construct that contains the gene encoding for IE180, designated pcDNAIE180. The DNA vaccine was delivered in gold microcarriers using a Helios Gene Gun, and 70% of BALB/c mice given the DNA vaccine (2 μg/mouse) seroconverted within 2 weeks. The remaining negative mice seroconverted after a single vaccine booster. Essentially similar results were obtained on vaccination of C57BL/6 mice, whereas C3H/HeJ mice remained negative after the first vaccination, but responded after a booster. Seven months after immunization with pcDNAIE180, an overall 25% of BALB/c, C3H/HeJ, and C57BL/6 mice receiving a lethal PrV challenge were protected. In addition, a significant passive transfer of IE180-specific antibodies to the offspring from pr...
TL;DR: Improvements in bias and efficiency are demonstrated when the different levels of exposure information are combined to estimate vaccine efficacy for reducing both susceptibility and infectiousness in an HIV vaccine trial.
Abstract: Exposure to infection information is important for estimating vaccine efficacy, but it is difficult to collect and inherently prone to missingness and mismeasurement. It is, therefore, generally not feasible to collect good exposure information on all participants in a large vaccine trial. We discuss study designs that collect detailed exposure information for only a small subset of trial participants, while collecting crude exposure information on all participants, and treat estimation of vaccine efficacy in the missing data/measurement error framework. We demonstrate with the example of an HIV vaccine trial the improvements in bias and efficiency when we combine the different levels of exposure information to estimate vaccine efficacy for reducing both susceptibility and infectiousness. We compare the performance of recently developed semi-parametric missing data methods of Pepe and Fleming and Carroll and Wand, Robins, Hsieh and Newey, and Reilly and Pepe.
TL;DR: Plans by a biotech company to begin so-called phase III trials of an HIV vaccine in the United States and Thailand have provoked strong reactions from AIDS researchers, who remain badly split over what kinds of vaccines are likely to work.
Abstract: AIDS RESEARCHPlans by a biotech company to begin so-called phase III trials of an HIV vaccine in the United States and Thailand have provoked strong reactions from AIDS researchers, who remain badly split over what kinds of vaccines are likely to work. And a report in the February issue of the Journal of Virology casts doubts on whether vaccines like the one to be used in the trials protect against HIV. The company does not yet have formal approval from U.S. or Thai authorities to proceed with phase III trials, but the U.S. Food and Drug Administration (FDA) has approved phase I and II trials--which test for safety and early signs of efficacy--of a modified version of a vaccine that has already gone through toxicity testing, and Thai authorities are expected to give their nod in the coming weeks. Moreover, a company representative says the FDA's vaccine advisory committee has given its blessing to its plans to move to phase III once these trials reconfirm the safety of the vaccine, which is made from a genetically engineered version of a protein called gp120 that makes up much of the outer coat of HIV.
TL;DR: Issues related to evaluating the direct protective effects of a vaccine in reducing susceptibility, VES, and its effect on reducing infectiousness, VEI are focused on.
Abstract: Several scientific questions are of interest in phase III trials of prophylactic human immunodeficiency virus (HIV) vaccines. In this paper we focus on some issues related to evaluating the direct protective effects of a vaccine in reducing susceptibility, VES, and its effect on reducing infectiousness, VEI. An estimation of VEI generally requires information on contacts between the infective and susceptible individuals. By augmenting the primary participants of an HIV vaccine trial by their steady sexual partners, information can be collected that allows an estimation of VEI as well as VES. Exposure to infection information, however, may be expensive and difficult to collect. A vaccine trial design can include a small validation set with good exposure to infection data to correct bias in a larger, simpler main study with only coarse exposure data. The large main study increases the efficiency of the small validation set. More research into the combination of different levels of information in vaccine trial design will yield more efficient and less biased estimates of the efficacy measures of interest.
Dissertation•
01 Jan 1998
TL;DR: The climate is right for behaviour change, and decrease in STD acquisition, in men in this setting, according to a cohort of HIV-1 seronegative male trucking company workers established in the Kenyan coastal city of Mombasa, and data on anticipated acceptance of the conditions of anAIDS preventive vaccine trial are presented.
Abstract: A cohort of HIV-1 seronegative male trucking company workers was established in the Kenyan coastal city of Mombasa, for the purposes of preparing them for HIV-1 preventive vaccine trials. The cohort was one of only three prospective male cohorts which have published data on heterosexual HIV-1 acquisition in sub-Saharan Africa, the continent most affected by this pandemic. HIV-1 seroincidence was measured and correlates of HIV-1 acquisition, including other STDs, were examined. Results of almost three year's of follow-up, and data on anticipated acceptance of the conditions of an HIV-1 vaccine trial are presented. o The baseline seroprevalence for antibodies to HIV-1 was 17% and the prevalence of active syphilis was 4.5%. o HIV-1 seroincidence was 4.0% per annum in 990 person years of follow-up. Multivariate Hazard analysis revealed a strong association between HIV-1 acquisition and occupation of driver or assistant (HR 4.0, 95% CI: 2.1-7.9), any sex with a partner other than a spouse (HR 4.2, 95% CI: 1.3-13.6), and a trend towards higher incidence with uncircumcised status (HR 2.0, 95% CI: 0.9-4.6). No association between STD and HIV-1 acquisition was found with an observed incidence of symptomatic gonococcal and non-gonococcal urethral discharge of 18.2% per annum, and 4.3% per annum for genital ulcer disease. o There were highly significant declines in extramarital sexual contacts from 50% to 40% in three month follow-up time blocks (p<0.001), and sex worker contacts from 12% to 6% (p=0.001), in a time trends analysis which included 494 person- years of follow-up. No significant change in condom use was recorded over time. Consistent (100%) condom use remained at approximately 30% of men engaging in extramarital sex with a partner other than a spouse. o Highly significant declines in the incidence of observed and reported sexually transmitted diseases were measured over the course of follow-up (p<0.001) in the first 494 person-years of follow-up. In the absence of data from the general population, it is not possible to attribute these declines to the behavioural and treatment interventions of the project, but it does document that the climate is right for behaviour change, and decrease in STD acquisition, in men in this setting. o Prevalence of symptomatic and asymptomatic urethral infections {N gonorrhoeae, C trachomatis, or T vaginalis) was 11.5% in a cross-sectional study which included HIV-1 seropositive men, following the documented decline in symptomatic STDs. Over two thirds of infections were asymptomatic. The leucocyte esterase dipstick (LED) urine screening test for urethral inflammation had a sensitivity of 55% and a specificity of 82%, in asymptomatic men. The LED test was the most accurate predictor of asymptomatic urethral infection. Risk assessment on the basis of demographic and behavioural characteristics did not prove useful. T vaginalis was the most common urethral infection and was associated with older age. o Eighty six per cent of 201 HIV-1 seronegative men interviewed in a vaccine acceptability survey stated that they felt at personal risk of HIV infection, and 84%) of men declared interest in participation in an HIV preventive vaccine trial. However, 17% of men stated that they would increase risk behaviour if they pai'ticipated in an HIV vaccine trial.
Journal Article•
TL;DR: The first full-scale clinical trial of an AIDS vaccine is scheduled to begin in June 1998 among volunteers in the US and Thailand, and animal studies of AIDSVAX have produced impressive results.
Abstract: The first full-scale clinical trial of an AIDS vaccine is scheduled to begin in June 1998 among volunteers in the US and Thailand. AIDSVAX manufactured by the US pharmaceutical company Vax Gen Inc. is based on the HIV envelope protein gp120 and stimulates antibody production. The US population will include 5000 homosexual men and a few uninfected heterosexuals with HIV-infected partners; two-thirds will be vaccinated over a 3-year period and the rest will be given a placebo. In Thailand 50% of a group of 2500 uninfected intravenous drug users will be vaccinated and the remaining participants will receive a placebo. Although animal studies of AIDSVAX have produced impressive results human studies to date have been less encouraging. In fact several researchers advise waiting for a more promising vaccine candidate. The efficacy of any vaccine that only boosts antibodies without also affecting T cells has been questioned.
TL;DR: Salient unresolved issues include the obligation of vaccine trial sponsors to make any successful vaccines available to the countries where they were tested, treatment for study participants who become infected, and the nature of HIV prevention programs for trial participants.
TL;DR: In your news article on the recent Geneva meeting to discuss ethical guidelines for AIDS vaccine trials, Adrian Ivinson concluded that a "hard-won consensus" was reached, and cited an article about the meeting that I wrote for Science, in which I reported precisely the opposite conclusion.
Abstract: In your news article on the recent Geneva meeting to discuss ethical guidelines for AIDS vaccine trials, Adrian Ivinson concluded that a "hard-won consensus" was reached. He also cited an article about the meeting that I wrote for Science, in which I reported precisely the opposite conclusion.
01 Jan 1998
TL;DR: This paper focuses on some issues related to evaluating the direct protective effects of a vaccine in reducing susceptibility, VEs, and its effect on reducing infectiousness, VE.
Abstract: Summary. Several scientific questions are of interest in phase IlIl trials of prophylactic human immunodeficiency virus (HIV) vaccines. In this paper we focus on some issues related to evaluating the direct protective effects of a vaccine in reducing susceptibility, VEs, and its effect on reducing infectiousness, VE,. An estimation of VE, generally requires information on contacts between the infective and susceptible individuals. By augmenting the primary participants of an HIV vaccine trial by their steady sexual partners, information can be collected that allows an estimation of VE, as well as VEs. Exposure to infection information, however, may be expensive and difficult to collect. A vaccine trial design can include a small validation set with good exposure to infection data to correct bias in a larger, simpler main study with only coarse exposure data. The large main study increases the efficiency of the small validation set. More research into the combination of different levels of information in vaccine trial design will yield more efficient and less biased estimates of the efficacy measures of interest.