Evaluation of a temperature-restricted, mucosal tuberculosis vaccine in guinea pigs

Tuhina Gupta; Monica LaGatta; Shelly Helms; Rebecca L Pavlicek; Simon O Owino; Kaori Sakamoto; Tamas Nagy; Stephen B Harvey; Mark Papania; Stephanie Ledden; Kevin T Schultz; Candace McCombs; Frederick D Quinn; Russell K Karls

doi:10.1016/j.tube.2018.10.006

Evaluation of a temperature-restricted, mucosal tuberculosis vaccine in guinea pigs

Tuberculosis (Edinb). 2018 Dec:113:179-188. doi: 10.1016/j.tube.2018.10.006. Epub 2018 Oct 19.

Authors

Affiliations

¹ Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
² Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA; Pathens, Inc., Athens, GA, USA.
³ Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
⁴ Animal Resources Program, University of Georgia, Athens, GA, USA; Department of Population Heath, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
⁵ Centers for Disease Control and Prevention, Atlanta, GA, USA.
⁶ Pathens, Inc., Athens, GA, USA.
⁷ Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA, USA; Pathens, Inc., Athens, GA, USA. Electronic address: [email protected].

Abstract

Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Guérin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.

Keywords: Intranasal; Mycobacterium; TBvac85; Tuberculosis; Vaccine.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acyltransferases / administration & dosage*
Acyltransferases / genetics
Acyltransferases / immunology
Administration, Intranasal
Aerosols
Animals
Antibodies, Bacterial / blood
Antigens, Bacterial / administration & dosage*
Antigens, Bacterial / genetics
Antigens, Bacterial / immunology
Bacterial Proteins / administration & dosage*
Bacterial Proteins / genetics
Bacterial Proteins / immunology
Disease Models, Animal
Female
Guinea Pigs
Immunity, Mucosal / drug effects*
Immunogenicity, Vaccine
Immunoglobulin G / blood
Lung / drug effects*
Lung / immunology
Lung / microbiology
Mycobacterium tuberculosis / drug effects*
Mycobacterium tuberculosis / immunology
Mycobacterium tuberculosis / pathogenicity
Nasal Mucosa / drug effects*
Nasal Mucosa / immunology
Nasal Mucosa / microbiology
Temperature
Time Factors
Tuberculosis Vaccines / administration & dosage*
Tuberculosis Vaccines / immunology
Tuberculosis, Pulmonary / blood
Tuberculosis, Pulmonary / immunology
Tuberculosis, Pulmonary / microbiology
Tuberculosis, Pulmonary / prevention & control*
Vaccination
Vaccines, DNA / administration & dosage

Substances

Aerosols
Antibodies, Bacterial
Antigens, Bacterial
Bacterial Proteins
Immunoglobulin G
Tuberculosis Vaccines
Vaccines, DNA
Acyltransferases
antigen 85B, Mycobacterium tuberculosis

Grants and funding

R41 AI100457/AI/NIAID NIH HHS/United States