Showing papers on "Vaccine trial published in 2006"
TL;DR: The vaccine HPV16 L1 VLP provides high-level protection against persistent HPV16 infection and HPV16-related CIN2–3 for at least 3.5 years after immunization, likely to reduce risk for cervical cancer.
480 citations
TL;DR: A multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one- half received hepatitis A vaccine, finding that aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections.
Abstract: BACKGROUND Acellular pertussis (aP) booster immunizations have been recommended for adolescents and older persons to enhance long-term protection and to possibly reduce community transmission of infections. METHODS This was a multicenter, randomized, double-blind vaccine trial in which one-half of the subjects received aP vaccine and one-half received hepatitis A vaccine (control subjects). All subjects were observed for almost 2 years for cough illnesses, and all underwent microbiologic and serologic studies for detection of pertussis infection. Immunoglobulin G (IgG) and immunoglobulin A (IgA) antibodies to pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae 2/3 were measured by enzyme-linked immunosorbent assay in serum samples obtained 1 and 12 months after immunization. Infection rates were determined with a variety of serologic criteria for control and vaccinated subjects. The incidence of prolonged cough illness was ascertained for subjects with and subjects without serologic evidence of infection. RESULTS Infection rates among control subjects are particularly representative of those in nonimmunized adults. Among control subjects, 0.4%-2.7% had increases in pertussis antibody of various types and degrees over 1 year, and 20%-46% had prolonged cough illnesses during this interval. Pertussis toxin antibody had the greatest specificity for detecting increases in antibody levels. Asymptomatic infections were approximately 5 times more common than clinical illnesses that met a strict clinical and microbiologic case definition. Relative to control subjects, aP-immunized subjects may have fewer increases in the antibody level (i.e., infections), especially for antibodies to fimbriae 2/3 (an antigen not in the vaccine). CONCLUSIONS Pertussis infections in older persons are largely asymptomatic. aP boosters confer protection for adolescents and adults against symptomatic pertussis and likely confer protection against mild and asymptomatic infections, and use of boosters may reduce transmission to others, especially infants.
121 citations
TL;DR: Human papillomavirus infection is a common sexually transmitted viral infection and is associated with the development of cervical cancer and it is likely that an HPV vaccine will become licensed for use in the near future.
Abstract: Aims: Human papillomavirus (HPV) infection is a common sexually transmitted viral infection and is associated with the development of cervical cancer. HPV vaccines are now undergoing phase 3 clinical trials in Australia. It is likely that an HPV vaccine will become licensed for use in the near future.
Methods: Ninety women aged 18–30 years from three different groups (those attending a dysplasia clinic, a local university health service and participants currently involved in a phase 3 HPV vaccine trial) completed a questionnaire assessing their knowledge base regarding HPV infection, cervical cancer, Pap tests and HPV vaccines.
Results: Respondents demonstrated good understanding of the Pap test and interpretation of an abnormal result. Most respondents (89%) had heard of HPV and attributed a number of different clinical symptoms to infection. For women who had not heard of an HPV vaccine, 79% of respondents stated that the most common resource they would use to obtain further information is their general practitioner.
Discussion: Many women do not understand the risk factors for HPV infection, the clinical problems it may cause and the potential long-term complications of infection. Few women have heard of a HPV vaccine, but most women surveyed would approach their general practitioner for more information if one became available.
Conclusion: This study highlights the need for further education regarding HPV infection and the potential long-term complications such as cervical cancer. It also demonstrates that education of general practitioners regarding an HPV vaccine is essential, as this is the most likely resource women will use to obtain further information in the future.
109 citations
TL;DR: 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 and future studies are warranted to define responders to immunotherapy.
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.
93 citations
TL;DR: A naturally occurring polymorphism (I → V at position 2, 2VGP2) associated with increased breast cancer risk was addressed and potential use in vaccination strategies was investigated.
Abstract: BACKGROUND
E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. The purpose of this study was to further investigate GP2 for potential use in vaccination strategies. Importantly, a naturally occurring polymorphism (I V at position 2, 2VGP2) associated with increased breast cancer risk was addressed.
METHODS
Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with autologous dendritic cells (DC) pulsed with GP2 and tested in standard cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 targets. Additional cytotoxicity experiments used effectors stimulated with DC pulsed with E75, GP2, or the combination of E75+GP2.
RESULTS
GP2-stimulated prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and the HLA-A2− control target SKOV3 of 28.8 ± 3.7% (P<.01), 29.5 ± 4.0% (P<.01), and 16.9 ± 2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells lysed HER2/neu+ targets at 43.8 ± 5.2% versus 44.2 ± 5.7% for E75 (P = .87). When combined, an additive effect was noted with 58.6 ± 5.4% lysis (P = .05). GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6 ± 5.7%) and 2VGP2-loaded T2 targets (17.7 ± 5.2%).
CONCLUSIONS
GP2 is a clinically relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; therefore, a GP2 vaccine should be effective in patients carrying this polymorphism. GP2 may be most beneficial used in a multiepitope vaccine. Cancer 2006. Published 2006 by the American Cancer Society.
80 citations
TL;DR: A vaccine trial has been designed to reassess the real protection afforded by these vaccines in face of recently isolated pathogenic strains, and results call for additional research for vaccine development and careful planning of strategies in the fight against CBPP.
Abstract: Contagious bovine pleuropneumonia is a major threat for cattle in Africa. Since 1956 the T1/44 strain has been used as a vaccine, and later on, T1sr, a streptomycin-resistant variant that gives fewer post-vaccinal reactions had been developed. These vaccines are known not to be very efficient but they normally should provide protection for about eight months. However, recent emergency vaccinations, performed in various countries in the southern part of the continent apparently met with failure, casting doubts on the identity as well as the protection afforded by the T1sr strain. A vaccine trial has been designed to reassess the real protection afforded by these vaccines in face of recently isolated pathogenic strains. Great care has been taken to test the original vaccinal strains at a dose corresponding to the minimum requirement by international standards. The test was performed in Cameroon, Kenya, and Namibia as to take into account the genetic diversity that exists among the pathogenic strains. In those conditions, the protection rate at three months varied from 33 to 67%, whatever the strain used, T1/44 or T1sr. These results call for additional research for vaccine development and careful planning of strategies in the fight against CBPP.
73 citations
TL;DR: In this article, the authors assess knowledge and attitudes of young uninsured women toward human papillomavirus vaccination and clinical trials and find that 72% of the respondents would enroll in a vaccine trial, despite the fact that 69% of women were ignorant of what HPV may cause, and only 10% acknowledged that HPV might lead to cervical cancer.
50 citations
TL;DR: It is found that vaccination of naïve mice with the multi-epitope vaccine, designated TD158, induced a strong HIV-1C-specific T-cell immune response, and that the addition of the Igkappa leader sequence to the TD158 vaccine construct significantly increased the frequencies of IFN-gamma secreting CD8+ T cells.
47 citations
TL;DR: In this paper, the authors present the findings of a qualitative investigation into the factors that may enable or inhibit participation in a future HIV vaccine trial in South Africa, using interviews and focus groups with trial site community members who had attended HIV vaccine education workshops.
Abstract: We present the findings of a qualitative investigation into the factors that may enable or inhibit participation in a future HIV vaccine trial. Thirty-seven semi-structured interviews and two focus groups were conducted with trial site community members who had attended HIV vaccine education workshops conducted by the community involvement programme of the South African AIDS Vaccine Initiative (SAAVI). Our findings indicate that enablers and inhibitors to participation in HIV vaccine trials may be further classified as either abstract or concrete. Each sub-theme was classified as an abstract inhibitor abstract enabler concrete inhibitor or concrete enabler. Abstract inhibitors were fear of illness or death lack of information about HIV/ AIDS and HIV vaccines and an HIV vaccine trials association with HIV/AIDS. Abstract enablers were participants reported sense of altruism and quality of life issues such as protection from becoming infected with HIV. Concrete inhibitors were the monetary costs associated with participation fear of being tested for HIV and receiving test results negative reactions from family and community members time delays between receiving trial participation information and actual enrolment and a general mistrust of researchers. Concrete enablers were practicalities and convenience financial rewards a safe testing environment positive family reactions to trial participation the different levels of participation available to different members of the community the salience of HIV in communities positive community reactions to vaccine trials and the presence of role models. In addition to these quadrants the enablers and inhibitors have also been located within a contextual framework that includes the individual family community and societal levels. Our research contributes to an understanding of the concerns of potential HIV vaccine trial participants within the South African context. Our findings illustrate the applicability of international research to proposed vaccine trial activities in South Africa and should therefore inform the development and implementation of successful community preparedness activities. (authors)
38 citations
TL;DR: Logistic regression modeling of the relationship between parasitemia and fever in data sets from Ghanaian children is used to determine the fraction of fevers attributable to malaria and to model how the choice of a threshold paras itemia in the clinical case definition affects the measured efficacy of malaria vaccines.
Abstract: Reported efficacies from vaccine trials may depend heavily on the clinical case definition used in the trial. The dependence may be particularly striking for diseases such as malaria, in which no single case definition is appropriate. We used logistic regression modeling of the relationship between parasitemia and fever in data sets from Ghanaian children to determine the fraction of fevers attributable to malaria and to model how the choice of a threshold parasitemia in the clinical case definition affects the measured efficacy of malaria vaccines. Calculated clinical attack rates varied 10-fold as a function of the threshold parasitemia. Strikingly, measured vaccine efficacies in reducing clinical malaria depended heavily on the threshold parasitemia, varying between 20% and 80% as the threshold varied between 1 and 5000 parasites/mL. We suggest that clinical case definitions of malaria that incorporate a threshold parasitemia are arbitrary and do not yield stable estimates of vaccine trial end points.
37 citations
TL;DR: The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific, indicating that blood-stage vaccines may play a role and merit further development.
Abstract: Background A malaria vaccine is needed because of the heavy burden of mortality and morbidity due to this disease. This review describes the results of trials of blood (asexual)-stage vaccines. Several are under development, but only one (MSP/RESA, also known as Combination B) has been tested in randomized controlled trials. Objectives To assess the effect of blood-stage malaria vaccines in preventing infection, disease, and death. Search strategy In March 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 1), MEDLINE, EMBASE, LILACS, and the Science Citation Index. We also searched conference proceedings and reference lists of articles, and contacted organizations and researchers in the field. Selection criteria Randomized controlled trials comparing blood-stage vaccines (other than SPf66) against P. falciparum, P. vivax, P. malariae, or P. ovale with placebo, control vaccine, or routine antimalarial control measures in people of any age receiving a challenge malaria infection. Data collection and analysis Both authors independently assessed trial quality and extracted data. Results for dichotomous data were expressed as relative risks (RR) with 95% confidence intervals (CI). Main results Five trials of MSP/RESA vaccine with 217 participants were included; all five reported on safety, and two on efficacy. No severe or systemic adverse effects were reported at doses of 13 to 15 microg of each antigen (39 to 45 microg total). One small efficacy trial with 17 non-immune participants with blood-stage parasites showed no reduction or delay in parasite growth rates after artificial challenge. In the second efficacy trial in 120 children aged five to nine years in Papua New Guinea, episodes of clinical malaria were not reduced, but MSP/RESA significantly reduced parasite density only in children who had not been pretreated with an antimalarial drug (sulfadoxine-pyrimethamine). Infections with the 3D7 parasite subtype of MSP2 (the variant included in the vaccine) were reduced (RR 0.38, 95% CI 0.26 to 0.57; 719 participants) while those with the other main subtype, FC27, were not (720 participants). Authors' conclusions The MSP/RESA (Combination B) vaccine shows promise as a way to reduce the severity of malaria episodes, but the effect of the vaccine is MSP2 variant-specific. Pretreatment for malaria during a vaccine trial makes the results difficult to interpret, particularly with the relatively small sample sizes of early trials. The results show that blood-stage vaccines may play a role and merit further development.
TL;DR: The inverse relationship between vaccine coverage and efficacy illustrates that people living in high-coverage areas may be indirectly protected from cholera because people living around them are vaccinated.
Abstract: Objectives The effectiveness of vaccines in populations must consider both direct and indirect protection. This study reanalyses data from a large individually randomized oral cholera vaccine trial that was conducted in rural Bangladesh from 1985 to 1990. A recent analysis of the results of that trial showed that the proportion of people in household clusters who received the vaccine was inversely related to placebo incidence during the first year of surveillance, which was attributed to herd immunity. Methods In this study we measure the relationship between neighbourhood-level oral cholera vaccine coverage and protective efficacy (PE) during a 2 year follow-up period, controlling for known effect modifiers. We link trial data to a household geographic information system to facilitate the neighbourhood-level analysis. Findings Neighbourhood-level PE can be partially explained by vaccine coverage after adjusting for ecological variables.
TL;DR: An assessment of community preparedness for HIV vaccine trials in the Democratic Republic of Congo seeks to identify factors that motivate a person to volunteer for a vaccine trial or which are disincentives to participation, along with preparedness of the larger community for trials.
Abstract: This paper reports on an assessment of community preparedness for HIV vaccine trials in the Democratic Republic of Congo. Formative research was conducted in the capital city of Kinshasa during the period October 2003 to March 2004 to answer questions pertinent to planning trials of a preventive HIV vaccine and to identify related issues. Twenty-seven in-depth interviews and two focus groups were held with potential trial participants and community leaders. Data was collected on the subjects of vaccines, HIV/AIDS and sexual behaviour, and an HIV vaccine. The study also sought to identify factors that motivate a person to volunteer for a vaccine trial or which are disincentives to participation, along with preparedness of the larger community for trials. Personal concerns for health and for the impact of the epidemic on families and country were common motivations for participation. The danger of an experimental vaccine and the stigma of a positive HIV antibody test as the result of vaccination are major concerns and disincentives. The health, educational, and local non-governmental sectors are identified as having important roles to play in assuring preparedness for trials, although significant challenges exist to achieving community preparedness.
TL;DR: The HIV epidemic is now spreading into every subpopulation depending on risk behaviors and shifting from specific risk groups to the general population.
Abstract: The first case of AIDS in Thailand was reported in September 1984. The number of newly reported AIDS cases increased every year peaking in 1998 with 27 528 cases. As of 31 December 2001 the year of the decision to conduct a phase III vaccine trial the cumulative number of reported AIDS cases was 196 373. Among those reported cases unsafe sex accounted for 85.6% the highest proportion by mode of transmission followed by intravenous drug use (3.9%) and mother-to-child transmission (3.3%). As of the end of 2004 the estimated number of HIV/AIDS cases is summarized in Table 1. The HIV epidemic is now spreading into every subpopulation depending on risk behaviors and shifting from specific risk groups to the general population. (excerpt)
TL;DR: A new HIV serodetection assay, termed HIV-SELECTEST, demonstrates >99% specificity and sensitivity, and in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within 1 to 3 months of HIV infection.
Abstract: All current human immunodeficiency virus (HIV) vaccine candidates contain multiple viral components and elicit antibodies that react positively in licensed HIV diagnostic tests, which contain similar viral products. Thus, vaccine trial participants could be falsely diagnosed as infected with HIV. Additionally, uninfected, seropositive vaccinees may encounter long-term social and economic harms. Moreover, this also interferes with early detection of true HIV infections during preventive HIV vaccine trials. An HIV-seropositive test result among uninfected vaccine trial participants is a major public health concern for volunteers who want to participate in future HIV vaccine trials. Based on the increased number of HIV vaccines being tested globally, it is essential to differentiate vaccine- from virus-induced antibodies. Using a whole-HIV-genome phage display library, we identified conserved sequences in Env-gp41 and Gag-p6 which are recognized soon after infection, do not contain protective epitopes, and are not part of most current HIV vaccines. We established a new HIV serodetection assay based on these peptides. To date, this assay, termed HIV-SELECTEST, demonstrates >99% specificity and sensitivity. Importantly, in testing of plasma samples from multiple HIV vaccine trials, uninfected trial participants scored negative, while all intercurrent infections were detected within 1 to 3 months of HIV infection. The new HIV-SELECTEST is a simple but robust diagnostic tool for easy implementation in HIV vaccine trials and blood banks worldwide.
TL;DR: A telephone survey to assess willingness to participate in HIV vaccine trials found that among the individuals interviewed, 37% would volunteer for a vaccine trial; those reporting high-risk behaviours were more likely to volunteer.
Abstract: We carried out a telephone survey to assess willingness to participate in HIV vaccine trials. The survey was conducted by interviewing randomly selected callers to the Italian National AIDS Help line. The questionnaire consisted of four sections: demographic information, knowledge about HIV vaccines and vaccines in general, factors related to participation in HIV vaccine trials, and acceptability of a future HIV vaccine. Over 50% of the sample had adequate knowledge about HIV and vaccines. Among the individuals interviewed, 37% would volunteer for a vaccine trial; those reporting high-risk behaviours were more likely to volunteer. Of the participants, 83% would agree to be vaccinated with a highly effective vaccine, and 92% would pay for the vaccine. Although the limits of telephone surveys should not be neglected, the results of this survey are encouraging.
TL;DR: This study frames the genetic diversity of HIV-1 in these cohorts in their preparatory phase for the ongoing ALVACHIV (vCP1521) prime, AIDSVAX B/E boost, phase III vaccine trial in Thailand and will provide a benchmark for interpretation and analysis.
Abstract: To characterize HIV-1 genotypes in candidate populations for a prime-boost phase III vaccine trial in Thailand, specimens from prevalent and incident HIV-1 infections from a family planning clinic population in Rayong Province and a community cohort in Chon Buri Province, collected from 1998 to 2001, were genotyped. A new multiregion hybridization assay, MHAbce, capable of distinguishing HIV-1 CRF01–AE, subtype B, and subtype C and their recombinants, was developed and applied to prevalent infections. Most incident and selected prevalent infections were studied by complete genome sequencing. By MHAbce, 168 of 194 prevalent infections were genotyped. Of these, 90.5% were CRF01–AE, 2.4% were subtype B, and 7.2% showed discordant or dual probe reactivity, indicative of recombination or dual infection, respectively. Among 23 incident infections, 20 were sequenced. Eighteen CRF01–AE, one subtype B, and one CRF01/B recombinant strains were seen. Two CRF01/B and one CRF01/C recombinant were identified among sele...
TL;DR: This editorial reviews the evidence for herdprotection and introduces new findings from the environmental studies on cholera to suggest a more complete understanding of the mechanisms for herd protection with cholERA vaccine.
Abstract: Recent analysis of results of the 1985 vaccine trial in Bangladesh showed that a killed oral cholera vaccine could provide herd protection (1), and this finding sheds new light on the potential utility of this vaccine and other oral cholera vaccines. Although there may be several mechanisms for herd protection, this finding of herd protection was somewhat unexpected. The nature of the herd protection with cholera vaccine is unlike that with live oral polio vaccine which can be excreted and can infect others, thereby immunizing persons who did not receive vaccine directly. By contrast, the cholera vaccine used in this study was inactivated, making it impossible for non-immunized persons to be immunized inadvertently. Another type of herd protection is seen with vaccine for Haemophilus influenzae type b in which the vaccination reduces respiratory carriage of the pathogen, thereby eradicating the reservoir and reducing transmission. Another example is that of measles vaccination which essentially stops transmission when the density of susceptible subjects is reduced below that needed to sustain transmission. Since cholera is transmitted directly from contaminated food or water, the finding of herd immunity seemed not entirely expected. This editorial reviews the evidence for herd protection and introduces new findings from the environmental studies on cholera to suggest a more complete understanding of the mechanisms for herd protection with cholera vaccine. Hopefully, by combining the observations of 'herd protection' with some newer concepts of 'herd amplification' coming from recent environmental studies, we may develop a better understanding of the most efficient ways to control cholera. A review of the evidence for herd protection The first suggestion of herd protection came from one analysis of the 1985 trial in which young children who had not received vaccine were about 50% less likely to be infected if their mothers had received vaccine (2). It was hypothesized that mothers receiving vaccine would have increased levels of antibody in their breastmilk and that these antibodies might protect their young children. However, the antibody titres in breastmilk of vaccinated mothers were not different from that in mothers who were given placebo. The protection observed without a corresponding elevation in breastmilk antibody titres suggested a different mechanism not associated specifically with protection from breastmilk antibodies. It seemed more likely that the immunized mothers were less likely to be colonized with Vibrio cholerae and pass this organism on to their children. Thus, the children had some protection from the vaccine, although they themselves were not vaccinated. More direct evidence of herd protection came from the recent re-analysis of the same 1985 field trial which combined GIS analysis with the data of cases occurring during the first year of the trial (1). The re-analysis included 89,596 people who were individually randomized and were immunized with B-subunit-whole cell (BS-WC) vaccine, the whole cell (WC) only vaccine, or a placebo. In this trial, both BS-WC and WC only vaccines were protective and thus, for this analysis, the vaccinated groups were combined. This new analysis was intended to determine if there was evidence of an indirect protective effect among the 6,423 geographic clusters depending on the proportion of persons in the clusters who had received one of the active vaccines (either the BS-WC or the WC only vaccine). It was hypothesized that an indirect effect of the vaccine would be manifested by lower incidence rates of cholera among recipients of placebo in clusters with higher levels of vaccine coverage. Since the randomization was by individual, the proportion of persons receiving an active vaccine varied widely between the different clusters, with proportions receiving active vaccine between 4% and 65% in the different clusters. For this analysis, the unit of the cluster is the bari which is a group of houses within the village. …
TL;DR: The efficiency of an inactivated tissue culture rabies vaccine produced on BHK-21 cells, according to an in-house developed process, was evaluated and compared to a commercial cell-tissue culture vaccine (Rabisin).
TL;DR: High-risk sexual behavior was reported by many VAX004 participants and controls, and differences between vaccine trial and control participants in the highest risk per contact behavior, receptive UAI with HIV-positive partners, was partly accounted for by perceived ART use.
Abstract: Objective: To assess and compare sexual behaviors using partner-specific data between HIV-negative men who have sex with men (MSM) recruited for an HIV vaccine efficacy trial and a control group. Methods: HIV-negative MSM from an HIV vaccine trial (n = 525) and controls (n = 732) were recruited by similar strategies and interviewed about behaviors with the 3 most recent partners in the past 6 months, obtained by audio computer-assisted self-interview (A-CASI). Results: Vaccine trial participants were more likely than controls to report an HIV-positive partner (24.7% and 14.1%, respectively) or an HIV-positive primary partner (16.1% and 6.8%, respectively) and were less likely to report occasional or single-time partners of unknown HIV status (51.6% and 63.2%, respectively; P < 0.05 for each comparison). Vaccine trial participants more often reported receptive unprotected anal intercourse (UAI) during their last sexual encounter with an HIV-positive partner (adjusted odds ratio [OR] = 2.7, 95% confidence interval [CI]: 1.0 to 7.9). Most believed their HIV-positive partners were receiving antiretroviral treatment (ART), however, and after adjustment for perceived ART use, the association between vaccine study participation and receptive UAI with an HIV-positive partner was not significant. Conclusions: High-risk sexual behavior was reported by many VAX004 participants and controls. Differences between vaccine trial and control participants in the highest risk per contact behavior, receptive UAI with HIV-positive partners, was partly accounted for by perceived ART use. Partner level data are useful in refining risk assessment, which is important in the evaluation of HIV vaccine and other prevention trials.
TL;DR: The rationale for TCR‐Id vaccines, the preclinical models as developed in the laboratory, and a discussion of the current plans for a vaccine trial in mycosis fungoides are reviewed.
Abstract: T cell lymphoproliferative disorders continue to be serious management problems, and so alternative therapeutic modalities are continuously being explored. One such strategy involves immunotherapy using the T cell receptor (TCR) as a target. Specifically we are attempting to develop a T cell receptor idiotype (TCR-Id) vaccine because the TCR-Id can serve as a tumor-specific antigen. In this article we will briefly review the rationale for TCR-Id vaccines, the preclinical models as developed in our laboratory, and a discussion of our current plans for a vaccine trial in mycosis fungoides.
TL;DR: The lack of a demonstrable antibody response to WNV vaccination in the flamingos may be attributable to the lack of species specificity of the vaccine, poorly developed immune system in 1-month-old flamingo chicks, poor sample handling or storage, or inadequate vaccine dose volume or frequency of administration.
Abstract: Greater flamingos (Phoenicopterus ruber ruber), an endangered and popular zoo bird species, are susceptible to West Nile virus (WNV) infection, often with a fatal outcome. To determine whether vaccination of greater flamingos produced an immunologic response with measurable antibody titers and to monitor for adverse effects of vaccination on health status, a vaccine trial against WNV infection, using a killed vaccine licensed for use in horses, was performed in 1-month-old flamingo chicks. Fifteen chicks determined to be seronegative for WNV were divided into 2 groups: Group A (n = 8) received 2, 1-ml IM doses of vaccine 3 weeks apart; and Group B (n = 7) received 1, 0.5-ml IM dose, followed by 2, 1-ml IM doses, all given 3 weeks apart. A booster vaccination of 1 ml was administered to all birds 280 days after the initial vaccination series. Antibody titers were measured after the initial immunization and before and 3 weeks after the booster vaccination by plaque-reduction neutralization testing ...
TL;DR: A conditional logistic regression model that accounts for within-randomization unit correlation over time is described, which models risk of disease as a function of community-level covariates and forms the covariates of interest for the investigation of indirect effects.
Abstract: When a sufficiently high proportion of a population is immunized with a vaccine, reduction in secondary transmission of disease can confer significant protection to unimmunized population members. We propose a straightforward method to estimate the degree of this indirect effect of vaccination in the context of a community-randomized vaccine trial. A conditional logistic regression model that accounts for within-randomization unit correlation over time is described, which models risk of disease as a function of community-level covariates. The approach is applied to an example data set from a pneumococcal conjugate vaccine study, with study arm and immunization levels forming the covariates of interest for the investigation of indirect effects.
TL;DR: It is concluded that immunizing infants against HIV-1 and participation in pediatric vaccine trials are generally acceptable to women at high risk for HIV- 1 infection.
Abstract: Vaccination of infants against human immunodeficiency virus type 1 (HIV-1) may prevent mother-to-child HIV-1 transmission. Successful trials and immunization efforts will depend on the willingness of individuals to participate in pediatric vaccine research and acceptance of infant HIV-1 vaccines. In a cross-sectional study, pregnant women presenting to a Nairobi antenatal clinic for routine care were interviewed regarding their attitudes toward participation in research studies and HIV-1 vaccine acceptability for their infants. Among 805 women, 782 (97%) reported they would vaccinate their infant against HIV-1 and 729 (91%) reported willingness to enroll their infant in a research study. However, only 644 (80%) would enroll their infants if HIV- 1 testing was required every 3 months and 513 (64%) would agree to HIV-1 vaccine trial participation. Reasons for not wanting to enroll in a pediatric HIV-1 vaccine trial included concerns about side effects (75%), partner objection (34%), and fear of discrimination (10%), HIV-1 acquisition (8%), or false-positive HIV-1 results (5%). The strongest correlate of pediatric vaccine trial participation was maternal willingness to be a vaccine trial participant herself; in univariate and multivariate models this was associated with a 17-fold increased likelihood of participation (HR 17.1; 95% CI 11.7-25; p < 0.001). We conclude from these results that immunizing infants against HIV-1 and participation in pediatric vaccine trials are generally acceptable to women at high risk for HIV-1 infection. It will be important to address barriers identified in this study and to include male partners when mobilizing communities for pediatric HIV-1 vaccine trials and immunization programs.
TL;DR: An experimental pig challenge system was readily able to confirm suboptimal performance of a commercial bacterin that had passed potency tests in mice but was associated with vaccine failure in commercial herds, and was also the most immunosuppressive to CMI responses associated with E. rhusiopathiae-specific and non-specific stimulation.
TL;DR: The HER2 p369-377/PLG vaccine plus adjuvant is safe and elicits HER2-specific T cells in patients with HER2 positive cancers.
Abstract: 2572 Background: Standard methods for immunization with peptides to elicit cytotoxic T lymphocytes (CTL) have not been well defined. Injection of soluble antigens in most standard vaccine formulati...
Journal Article•
TL;DR: Results from six randomized controlled trials of monvalent, bivalent and quadrivalent prophylactic HPV recombinant vaccines demonstrated high-level protection from infection and lesions caused by the targeted HPV types, finding the vaccines to be generally safe and well-tolerated.
Abstract: CS21-01 Results from six randomized controlled trials of monvalent (HPV16), bivalent (HPV16/18) and quadrivalent (HPV6/11/16/18) prophylactic HPV recombinant vaccines demonstrated high-level protection from infection and lesions caused by the targeted HPV types. The vaccines were found to be generally safe and well-tolerated. The quadrivalent HPV6/11/16/18 vaccine (Gardasil®, Merck, USA), has been licensed in many countries for use among females between 9 and 26 years of age. The bivalent HPV16/18 vaccine (Cervarix™, GlaxoSmithKline, Belguim) is currently under review for licensure in Europe and soon will be submitted for review in other countries. Both vaccines, which are composed of empty viral capsids called virus-like-particles (VLP), have the potential to substantially reduce HPV-related morbidity and mortality. HPV16 and HPV18 cause about 70% of cervical cancers, 80% to 90% of anal cancers, 40% of vulvar cancers, 15% to 20% of head and neck cancers and an uncertain proportion of penile, vaginal, and urethral cancers worldwide. HPV6 and HPV11 cause at least 80% of genital warts and over 95% of a rare, but highly morbid condition called recurrent respiratory papillomatosis. Additional vaccine trial findings show that protection is durable for at least 4 to 5 years. Evidence of vaccine efficacy among young men and women older than 26 years will be available within the next couple of years. Now that prevention of many HPV-related cancers and intraepithelial lesions through vaccination has become a possibility, it is important to develop recommendations that are based on current and evolving knowledge of the optimal ages for routine and "catch-up vaccination, need for boosters, role of herd immunity, barriers to implementation, and impact on cervical cancer screening programs.