Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings

Abstract

On April 9, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "Developing Aerosol Vaccines for Mycobacterium tuberculosis" in Bethesda, MD. The purpose of the meeting was to explore the potential for developing aerosol vaccines capable of preventing infection with M. tuberculosis (Mtb), preventing the development of active tuberculosis (TB) among those latently infected with Mtb, or as immunotherapy for persons with active TB. The workshop was organized around four key questions relevant to developing and assessing aerosol TB vaccines: (1) What is the current knowledge about lung immune responses and early pathogenesis resulting after Mtb infection and what are the implications for aerosol TB vaccine strategies? (2) What are the technical issues surrounding aerosol vaccine delivery? (3) What is the current experience in aerosol TB vaccine development? and (4) What are the regulatory implications of developing aerosol vaccines, including those for TB? Lessons learned from the WHO effort to develop an aerosol measles vaccine served as a case example for overall discussions at the meeting. Workshop participants agreed that aerosol delivery represents a potentially important strategy in advancing TB vaccine development efforts. As no major regulatory, manufacturing or clinical impediments were identified, members of the workshop emphasized the need for greater support to further explore the potential for this delivery methodology, either alone or as an adjunct to traditional parenteral methods of vaccine administration.

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

“…The use of vaccine formulations that induce local immune responses in the lungs could be an interesting approach. Interest in lung vaccination has recently increased for prevention and treatment of respiratory diseases such as tuberculosis and influenza [ 4 – 6 ]. Besides the induction of local immune responses, vaccines targeting the lungs would have other advantages over parenteral injection, such as no risks of needle injuries and removal of cold chain requirements in the case of dry powder formulations [ 7 ].…”

Prophylaxis of Mycobacterium tuberculosis H37Rv Infection in a Preclinical Mouse Model via Inhalation of Nebulized Bacteriophage D29

“…needed (1). Vaccines against M. tuberculosis are an active area of research (1,(3)(4)(5)(6), and indeed, much of the global community receives Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination against TB as youth. BCG and other vaccine candidates can induce limited prophylactic protection through adolescence (7); however, BCG provides limited-to-no prophylactic effect if given to adults, does not prevent reactivation of latent TB, and does not prevent M. tuberculosis transmission (8,9).…”

Repeated Aerosolized-Boosting with Gamma-Irradiated Mycobacterium bovis BCG Confers Improved Pulmonary Protection against the Hypervirulent Mycobacterium tuberculosis Strain HN878 in Mice

“…Furthermore, it was suggested that aerosol delivery of a TB vaccine directly to the respiratory mucosa might offer physiological and immunological benefits [ 34 ]. Although these potential benefits of aerosol TB vaccine strategies have recently been emphasized, there is still a lack of technical and practical means of applying aerosol delivery-based TB vaccines [ 35 ].…”

“…The main strategy of a mucosal vaccine in TB is controlling the early phase of Mtb growth, as there remains an interval of approximately 12 days from infection to the activation of host T cell responses induced by parental immunization [ 35 , 50 ]. Considering that the containment of Mtb is mediated by lung-resident memory lymphocytes [ 51 ], we believe that our strategy may shorten this interval.…”