Gilbert PB, Chiu YL, Allen M, Lawrence DN, Chapdu C, Israel H et al.Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials. Vaccine 21:2933-2947
This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.
"In addition, PCPP has been safely tested in Phase I clinical trials as an adjuvant with an influenza vaccine on young and elderly human adults with enhanced immune responses in sera and no side effects . PCPP also been used in clinical trials on a HIV vaccine . Clinical studies of PCEP have yet to be reported. "
[Show abstract][Hide abstract] ABSTRACT: We previously demonstrated that polyphosphazenes, particularly PCEP, enhance immune responses in mice immunized subcutaneously and intranasally. The objective of the present study was to investigate the efficacy of polyphosphazenes as adjuvants when delivered through different routes of vaccine administration.
BALB/c mice were immunized through intranasal, subcutaneous, oral and intrarectal delivery with vaccine formulations containing either influenza X:31 antigen alone or formulated in PCEP. Serum and mucosal washes were collected and assayed for antigen-specific antibody responses by ELISA, while splenocytes were assayed for antigen-specific cytokine production by ELISPOT.
Intranasal immunization with PCEP+X:31 induced significantly higher IgA titers in all mucosal secretions (lung, nasal, and vaginal) compared to the other routes. Serum analysis showed that all mice given the PCEP+X:31 combination showed evidence of enhanced IgG2a titers in all administered routes, indicating that PCEP can be effective as an adjuvant in enhancing systemic immune responses when delivered via different routes of administration.
We conclude that PCEP is a potent and versatile mucosal adjuvant that can be administered in a variety of routes and effectively enhances systemic and local immune responses. Furthermore, intranasal immunization was found to be the best administration route for enhancing IgA titers, providing further evidence for the potential of PCEP as a mucosal adjuvant.
Journal of Immune Based Therapies and Vaccines 08/2010; 8(1):4. DOI:10.1186/1476-8518-8-4
"HVTN clinical staff code adverse events into MedDRA lower level terms, which are then linked to MedDRA body system and preferred terms for reporting. A comprehensive summary of safety events in NIAID-sponsored Phase I and II HIV-1 vaccine trials can be found in Ref.  "
[Show abstract][Hide abstract] ABSTRACT: The HIV pandemic is a pressing threat to global public health; HIV vaccine development is critical. Clinical evaluation of HIV vaccine candidates differs from the standard therapeutics trial framework primarily due to the fact that healthy individuals are studied. We present an early stage evaluation program developed for the HIV Vaccine Trials Network (HVTN) motivated by characteristics unique to the vaccine setting. The program consists of 3 prototypical stages (Phase I, Ib, II) that provide a unified yet flexible approach to the safety and immunogenicity evaluation of diverse vaccine regimens. The goal of these early trials is to narrow the number of candidate vaccines to the most promising candidates worthy of further study in efficacy trials.
"These papers are not consistent with each other, and the more frequently cited study, by Oh et al., has serious design flaws that may cast doubt on the gp120 concentrations it promulgates. The much lower gp120 concentrations recorded by Gilbert et al. (2003) are likely to be closer to true levels. And the presence of plasma anti-gp120 Abs that block receptor binding should inform the design of in vitro experiments (see Box 1). "
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