There is a need for an improved vaccine to better control human tuberculosis (TB), as the only currently available TB vaccine, bacillus Calmette-Guerin (BCG) delivered parenterally, offers variable levels of efficacy. Therefore, recombinant strains expressing additional antigens are being developed alongside alternative routes to parenteral delivery. There is strong evidence that BCG Moreau (RdJ) is a safe and effective vaccine in humans when given by the oral route. This study compared the efficacy of a single oral dose of wild type BCG Moreau Rio de Janeiro (RdJ), or a recombinant RdJ strain expressing Ag85B-ESAT6 fusion protein, formulated with and without lipid to enhance oral delivery, with subcutaneous BCG Danish 1331 and saline control groups in a guinea pig aerosol infection model of pulmonary tuberculosis. Protection was measured as survival at 30 weeks post-challenge and reduced bacterial load and histopathology in lungs and spleen. Results showed that a single oral dose of BCG Moreau (RdJ) or recombinant BCG Moreau (RdJ)-Ag85B-ESAT6, formulated with or without lipid, gave protection equivalent to subcutaneously delivered BCG Danish in the 30 weeks post-challenge survival study. The orally delivered vaccines gave reduced pathology scores in the lungs (three of the four formulations) and spleens (all four formulations) compared to subcutaneously delivered BCG Danish. The oral wild type BCG Moreau (RdJ) in lipid and the unformulated oral wild type BCG Moreau (RdJ) vaccine also gave statistically lower bacterial loads in the lungs and spleens, respectively, compared to subcutaneously delivered BCG Danish. This study provides further evidence to show that lipid formulation does not impair vaccine efficacy and may enhance the delivery and stability of oral vaccines intended for use in countries with poor health infrastructure. Oral delivery also avoids needles (and associated cross-infection risks) and immunisation without the need for specially trained medical professional staff.
Bibliographical noteFunding Information:
This work was funded by the European Commission (Mucosal Vaccines for Poverty Related Diseases, European Union Contract LSHP-CT-2003-503240) and the Department of Health (UK) . The views expressed in this publication are those of the authors and not necessarily those of the funding bodies. We thank Rino Rappuoli and Donata Medaglini for support. We are grateful to Jes Dietrich and Peter Andersen for sharing recombinant antigens with us and to Frank Aldwell for the provision of lipid for oral formulations. We thank Susan Gray (CEPR) for histopathological processing and Graham Hall (CEPR) for histological analysis and generation of macroimages. The staff in the Biological Investigations Group at HPA, CEPR Porton Down, are sincerely thanked for their technical support.
- BCG Moreau
- Lipid formulation
- Oral delivery