Randomized Phase I: Safety, Immunogenicity and Mucosal Antiviral Activity in Young Healthy Women Vaccinated with HIV-1 Gp41 P1 Peptide on Virosomes.

UNLABELLED: Mucosal antibodies harboring various antiviral activities may best protect mucosal surfaces against early HIV-1 entry at mucosal sites and they should be ideally induced by prophylactic HIV-1 vaccines for optimal prevention of sexually transmitted HIV-1. A phase I, double-blind, randomized, placebo-controlled trial was conducted in twenty-four healthy HIV-uninfected young women. The study objectives were to assess the safety, tolerability and immunogenicity of virosomes harboring surface HIV-1 gp41-derived P1 lipidated peptides (MYM-V101). Participants received placebo or MYM-V101 vaccine at 10 µg/dose or 50 µg/dose intramuscularly at week 0 and 8, and intranasally at week 16 and 24. MYM-V101 was safe and well-tolerated at both doses administered by the intramuscular and intranasal routes, with the majority of subjects remaining free of local and general symptoms. P1-specific serum IgGs and IgAs were induced in all high dose recipients after the first injection. After the last vaccination, vaginal and rectal P1-specific IgGs could be detected in all high dose recipients. Approximately 63% and 43% of the low and high dose recipients were respectively tested positive for vaginal P1-IgAs, while 29% of the subjects from the high dose group tested positive for rectal IgAs. Serum samples had total specific IgG and IgA antibody concentrations ≥ 0.4 µg/mL, while mucosal samples were usually below 0.01 µg/mL. Vaginal secretions from MYM-V101 vaccinated subjects were inhibiting HIV-1 transcytosis but had no detectable neutralizing activity. P1-specific Th1 responses could not be detected on PBMC. This study demonstrates the excellent safety and tolerability of MYM-V101, eliciting systemic and mucosal antibodies in the majority of subjects. Vaccine-induced mucosal anti-gp41 antibodies toward conserved gp41 motifs were harboring HIV-1 transcytosis inhibition activity and may contribute to reduce sexually-transmitted HIV-1. TRIAL REGISTRATION: ClinicalTrials.gov NCT01084343.

Potential and limitation of UVC irradiation for the inactivation of pathogens in platelet concentrates.

BACKGROUND: Pathogen contamination, causing transfusion-transmitted diseases, is an ongoing concern in transfusion of cellular blood products. In this explorative study, the pathogen-inactivating capacity of UVC irradiation in platelet (PLT) concentrates was investigated. The dose dependencies of inactivation of several viruses and bacteria were compared with the effect on PLT quality. STUDY DESIGN AND METHODS: The potential of UVC irradiation was studied with a range of lipid-enveloped (LE) and non-lipid-enveloped viruses (NLE) and bacteria. LE viruses were bovine viral diarrhea virus (BVDV), human immunodeficiency virus (HIV), pseudorabies virus (PRV), transmissible gastroenteritis virus (TGEV), and vesicular stomatitis virus (VSV). NLE viruses were canine parvovirus (CPV) and simian virus 40 (SV40). Bacteria were Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Bacillus cereus. After spiking and irradiation, samples were tested for residual infectivity and reduction factors (RFs) were calculated. Furthermore, the effect of UVC irradiation on PLT quality was determined by measuring in vitro quality variables. RESULTS: A UVC dose of 500 J per m(2) resulted in acceptable PLT quality (as measured by pH, lactate production, CD62P expression, and exposure of phosphatidylserine) and high RFs (>4 log) for CPV, TGEV, VSV, S. epidermidis, S. aureus, and E. coli. Intermediate RFs (approx. 3 log) were observed for BVDV, PRV, and B. cereus. Low RFs (approx. 1 log) were found for HIV and SV40. No differences in virus reduction were observed between cell-free and cell-associated virus. CONCLUSION: UVC irradiation is a promising pathogen-reducing technique in PLT concentrates, inactivating bacteria, and a broad range of viruses (with the exception of HIV) under conditions that have limited effects on PLT quality. Further optimization of the UVC procedure, however, is necessary to deal with blood-borne viruses like HIV.

Inhibition of HIV-1 IIIB and clinical isolates by human parotid, submandibular, sublingual and palatine saliva.

Human saliva is known to possess components that decrease the HIV-1 infectivity in vitro. The mechanism of how these components inhibit the infectivity is still not clear on the molecular level. The purpose of this study was to discriminate between serous and mucous components with respect to inhibitory capacity and site of action. We have used total saliva and saliva from the major (sero)mucous glands: submandibular gland, sublingual glands, and glands in the palate, in comparison with the serous parotid glands. HIV-1 IIIB and primary variants were incubated with saliva, and inhibition of HIV-1-infection was determined by analysing the cytopathic effect on MT-2 cells. Mucous saliva, as well as serous saliva, contained high molecular weight components that reduced HIV-1-infectivity, at least partially by entrapment of the virus particles. Lower molecular weight components in all types of saliva possessed strong HIV-1 neutralizing capacity. Using pro-viral DNA synthesis by reverse transcription as a discrimination point in the replication cycle, the results indicated that part of the saliva samples acted before, but others after, this point. In conclusion, saliva inhibits HIV-1-infection by the action of high molecular weight components in combination with low molecular weight components from serous as well as mucous saliva, affecting different stages of the infection cycle.