• Arístides Aguilar Betancourt, C A González Delgado, Z Cinza Estévez, J Cabrera Martínez, G Véliz Ríos, S R Moreno Aureoles-Roselló, R Alemán Zaldívar, M Alonso Guzmán, N Figueroa Baile, P A Días Reyes, L Olivera Ruano, A Correa Fernández, Y Lobaina-Matos, A Delahanty Fernández, A I Juvier Madrazo, M I Alonso Martínez, M Lago Baños, N Puble Alvarez, M David Baldo, R E Soto Mestre, M V Pérez Pérez, M E Peña Martínez, D Acosta Escobar, M J Cerna Guanche, L Mila Cáceres, R Sánchez Betancourt, E Hardy Rando, G E Guillén Nieto, V L Muzio González, and J C Aguilar Rubido.
• Vaccine Division, Vaccine Clinical Trials Department, Center for Genetic Engineering and Biotechnology, PO Box 6162, Cubanacán, Playa, Havana City, Cuba. aristides.aguilar@cigb.edu.cu
• Int. J. Infect. Dis. 2007 Sep 1; 11 (5): 394-401.

BackgroundThe 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 50 microg HBsAg and 50 microg 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 0.5 ml was administered in two dosages of 125 microl per nostril. Adverse events were actively recorded 1 h, 6 h, 12 h, 24 h, 48 h, 72 h, 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 (>or=10 IU/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.

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