A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques

Kara Jensen, Uma Devi K Ranganathan, Koen K A Van Rompay, Don R. Canfield, Imran Khan, Resmi Ravindran, Paul A. Luciw, William R. Jacobs, Glenn Fennelly, Michelle H. Larsen, Kristina Abel

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV andM. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV andM. tuberculosis infections is urgently needed. We hypothesized that a highly attenuatedM. tuberculosis strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immuno-compromised hosts. Of three vaccine candidates tested, the recombinant attenuatedM. tuberculosis strain mc 26435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative ofM. tuberculosis infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuatedM. tuberculosis-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.

Original languageEnglish (US)
Pages (from-to)1170-1181
Number of pages12
JournalClinical and Vaccine Immunology
Volume19
Issue number8
DOIs
StatePublished - Aug 2012

Fingerprint

Tuberculosis Vaccines
Simian Immunodeficiency Virus
Macaca
Viruses
Mycobacterium tuberculosis
HIV
Tuberculosis
Vaccines
Bacillus
Pediatrics
Bacilli
Infection
BCG Vaccine
Immune Evasion
Safety
Mucosal Immunity
Virus Diseases
Mycobacterium bovis
Acquired Immunodeficiency Syndrome
Plasmids

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Immunology
  • Immunology and Allergy
  • Microbiology (medical)

Cite this

A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques. / Jensen, Kara; Ranganathan, Uma Devi K; Van Rompay, Koen K A; Canfield, Don R.; Khan, Imran; Ravindran, Resmi; Luciw, Paul A.; Jacobs, William R.; Fennelly, Glenn; Larsen, Michelle H.; Abel, Kristina.

In: Clinical and Vaccine Immunology, Vol. 19, No. 8, 08.2012, p. 1170-1181.

Research output: Contribution to journalArticle

Jensen, Kara ; Ranganathan, Uma Devi K ; Van Rompay, Koen K A ; Canfield, Don R. ; Khan, Imran ; Ravindran, Resmi ; Luciw, Paul A. ; Jacobs, William R. ; Fennelly, Glenn ; Larsen, Michelle H. ; Abel, Kristina. / A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques. In: Clinical and Vaccine Immunology. 2012 ; Vol. 19, No. 8. pp. 1170-1181.
@article{6a335a88fc2f4e16b72ae331459eb4ec,
title = "A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques",
abstract = "Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV andM. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Gu{\'e}rin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV andM. tuberculosis infections is urgently needed. We hypothesized that a highly attenuatedM. tuberculosis strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immuno-compromised hosts. Of three vaccine candidates tested, the recombinant attenuatedM. tuberculosis strain mc 26435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative ofM. tuberculosis infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuatedM. tuberculosis-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.",
author = "Kara Jensen and Ranganathan, {Uma Devi K} and {Van Rompay}, {Koen K A} and Canfield, {Don R.} and Imran Khan and Resmi Ravindran and Luciw, {Paul A.} and Jacobs, {William R.} and Glenn Fennelly and Larsen, {Michelle H.} and Kristina Abel",
year = "2012",
month = "8",
doi = "10.1128/CVI.00184-12",
language = "English (US)",
volume = "19",
pages = "1170--1181",
journal = "Clinical and Vaccine Immunology",
issn = "1556-6811",
publisher = "American Society for Microbiology",
number = "8",

}

TY - JOUR

T1 - A recombinant attenuated Mycobacterium tuberculosis vaccine strain is safe in immunosuppressed simian immunodeficiency virus-infected infant macaques

AU - Jensen, Kara

AU - Ranganathan, Uma Devi K

AU - Van Rompay, Koen K A

AU - Canfield, Don R.

AU - Khan, Imran

AU - Ravindran, Resmi

AU - Luciw, Paul A.

AU - Jacobs, William R.

AU - Fennelly, Glenn

AU - Larsen, Michelle H.

AU - Abel, Kristina

PY - 2012/8

Y1 - 2012/8

N2 - Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV andM. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV andM. tuberculosis infections is urgently needed. We hypothesized that a highly attenuatedM. tuberculosis strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immuno-compromised hosts. Of three vaccine candidates tested, the recombinant attenuatedM. tuberculosis strain mc 26435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative ofM. tuberculosis infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuatedM. tuberculosis-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.

AB - Many resource-poor countries are faced with concurrent epidemics of AIDS and tuberculosis (TB) caused by human immunodeficiency virus (HIV) and Mycobacterium tuberculosis, respectively. Dual infections with HIV andM. tuberculosis are especially severe in infants. There is, however, no effective HIV vaccine, and the only licensed TB vaccine, the Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccine, can cause disseminated mycobacterial disease in HIV-infected children. Thus, a pediatric vaccine to prevent HIV andM. tuberculosis infections is urgently needed. We hypothesized that a highly attenuatedM. tuberculosis strain containing HIV antigens could be safely administered at birth and induce mucosal and systemic immune responses to protect against HIV and TB infections, and we rationalized that vaccine safety could be most rigorously assessed in immuno-compromised hosts. Of three vaccine candidates tested, the recombinant attenuatedM. tuberculosis strain mc 26435 carrying a simian immunodeficiency virus (SIV) Gag expression plasmid and harboring attenuations of genes critical for replication (panCD and leuCD) and immune evasion (secA2), was found to be safe for oral or intradermal administration to non-SIV-infected and SIV-infected infant macaques. Safety was defined as the absence of clinical symptoms, a lack of histopathological changes indicative ofM. tuberculosis infection, and a lack of mycobacterial dissemination. These data represent an important step in the development of novel TB vaccines and suggest that a combination recombinant attenuatedM. tuberculosis-HIV vaccine could be a safe alternative to BCG for the pediatric population as a whole and, more importantly, for the extreme at-risk group of HIV-infected infants.

UR - http://www.scopus.com/inward/record.url?scp=84864572318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864572318&partnerID=8YFLogxK

U2 - 10.1128/CVI.00184-12

DO - 10.1128/CVI.00184-12

M3 - Article

C2 - 22695156

AN - SCOPUS:84864572318

VL - 19

SP - 1170

EP - 1181

JO - Clinical and Vaccine Immunology

JF - Clinical and Vaccine Immunology

SN - 1556-6811

IS - 8

ER -