Pre-clinical and clinical investigation of the safety of a novel adjuvant for intranasal immunization

Nasalflu Berna is a trivalent influenza virus vaccine for active immunization against influenza by the nasal route. It consists of influenza virosomes which are formulated from inactivated influenza strains and heat-labile toxin from aseptic Escherichia coli bacteria strain, as an adjuvant (HIT). The results of preclinical studies in ferrets, baboons, minipigs, mice and rabbits are presented here, and issues concerning route of administration, mechanism of action (preventing the disease and halting further spread of the disease), and the specific safety issues of the adjuvant itself (possible neurological activity of HLT) are examined. No clinical signs were detected in the animals, and hematological values were in the normal range. In particular, there was no evidence of any systemic adverse reaction, including sensitization to the test substances, and no evidence of possible neurological activity of the HLT. Further clinical studies in humans conducted over five influenza seasons using this virosome-formulated intranasal vaccine, elicited high levels of influenza-specific hemagglutination inhibition IgG antibody titers to the strains incorporated in the administered vaccine. In addition, I-A antibodies were also elicited in the nasal mucosa, and in the saliva. In addition to the systemic IgG antibody titers, the nasal mucosal I-A antibody response may provide additional local protection by the inhibition of viral replication and further spread in the respiratory tract. Nasalflu was well tolerated by most of the vaccinated subjects, both in terms of nasal symptoms and possible vaccination-mediated systemic symptoms. Both local and systemic symptoms were primarily mild, with only an occasional subject reporting moderate intensity. Out of four serious adverse events seen during the clinical development, only one was thought to be remotely related to the test vaccine. Nasalflu, developed by the Swiss Serum and Vaccine Institute, is a novel, highly immunogenic and safe influenza subunit vaccine which is easily administered as a nasal spray. This new route of administration is likely to increase compliance to vaccination, and could become an important tool to promote vaccination in population groups which show high resistance to vaccination. (C) 2001 Elsevier Science Ltd. All rights reserved.