DEVELOPMENT OF BORDETELLA PERTUSSIS AS A UNIVERSAL INFLUENZA VACCINE DELIVERY SYSTEM AND APPLICATION AS A LIVE PERTUSSIS VACCINE

Abstract

The threat of a pandemic spread of highly virulent influenza A viruses currently represents a top global public health problem. Mass vaccination remains the cornerstone of influenza prevention. Current vaccination strategies face the challenge to meet the demands in a pandemic situation. The potential emergence of an influenza pandemic at any time combined with limited vaccine supplies, have rendered the development of novel universal influenza vaccines that would provide cross-clade protective immunity a public health priority. As a strict human pathogen that naturally infects the respiratory tract, Bordetella pertussis is particularly well-adapted for the nasal delivery of heterologous vaccine candidates and represents a promising mucosal vaccine delivery system when suitably attenuated. In addition, ideally immunization with recombinant B. pertussis bacteria should provide a concomitant protection against both pertussis and the target disease. A highly attenuated B. pertussis strain, named BPZE1, has been described in which three toxins have been genetically inactivated. Despite a markedly reduced lung inflammation, BPZE1 is able to colonize the murine lungs efficiently and induce a strong protective immune response. BPZE1 has recently completed a phase I clinical trial in adult human volunteers as a nasal live pertussis vaccine candidate.