Phase I clinical trial in healthy adults of a nasal vaccine candidate containing recombinant hepatitis B surface and core antigens

SummaryBackgroundThe nasal vaccine candidate (NASVAC), comprising hepatitis B virus (HBV) surface (HBsAg) and core antigens (HBcAg), has been shown to be highly immunogenic in animal models.MethodsA phase I double-blinded, placebo-controlled randomized clinical trial was carried out in 19 healthy male adults with no serologic markers of immunity/infection to HBV. This study was aimed at exploring the safety and immunogenic profile of nasal co-administration of both HBV recombinant antigens. The trial was performed according to Good Clinical Practice guidelines. Participants ranged in age from 18 to 45 years and were randomly allocated to receive a mixture of 50μg HBsAg and 50μg HBcAg or 0.9% physiologic saline solution, as a placebo, via nasal spray in a five-dose schedule at 0, 7, 15, 30, and 60 days. A total volume of 0.5ml was administered in two dosages of 125μl per nostril. Adverse events were actively recorded 1h, 6h, 12h, 24h, 48h, 72h, 7 days and 30 days after each dose. Anti-HBs and anti-HBc titers were evaluated using corresponding ELISA kits at days 30 and 90.ResultsThe vaccine candidate was safe and well tolerated. Adverse reactions included sneezing (34.1%), rhinorrhea (12.2%), nasal stuffiness (9.8%), palate itching (9.8%), headache (9.8%), and general malaise (7.3%). These reactions were all self-limiting and mild in intensity. No severe or unexpected events were recorded during the trial. The vaccine elicited anti-HBc seroconversion in 100% of subjects as early as day 30 of the immunization schedule, while a seroprotective anti-HBs titer (≥10IU/l) was at a maximum at day 90 (75%). All subjects in the placebo group remained seronegative during the trial.ConclusionThe HBsAg–HBcAg vaccine candidate was safe, well tolerated and immunogenic in this phase I study in healthy adults. To our knowledge, this is the first demonstration of safety and immunogenicity for a nasal vaccine candidate comprising HBV antigens

In vitro antimicrobial activity of total extracts of the leaves of Petiveria alliacea L. (Anamu)

The antimicrobial activity of 13 total extracts was evaluated, 10 soft extracts (B) and 3 blended extracts (E) prepared from dry and fresh leaves of Petiveria alliacea L. Various solvents were used for their preparation: hydroalcoholic solution at 30%, 80% and isopropyl alcohol. The antimicrobial effect of the extracts was tested by means of the method of Kirby-Bauer, using four bacterial strains from the ATCC collection (Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa) and a leveduriform fungus (Candida albicans). The following quality control parameters were determined for most active extracts: physical, physical-chemical and chemical parameters. The results were: nine extracts showed antibacterial activity, being the most concentrated (B8 and E3), the ones with the highest activity in the presence of the bacteria tested; the effect of blended extracts (E1, E2 and E3) was greater in the presence of P. aeruginosa. Blended extracts are considered more potent and active than soft extracts. No antifungal activity was obtained for both types of extracts. The Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were determined for both extracts, with the following results: MIC-soft extracts (>100 mg/mL), blended extracts (>50 mg/mL); MBC-soft extracts (≥400 mg/mL), blended extracts (≥200 mg/mL) based on fresh leaves