Enhanced Immunogenicity and Protective Efficacy Against <i>Mycobacterium tuberculosis</i> of Bacille Calmette-Guérin Vaccine Using Mucosal Administration and Boosting with a Recombinant Modified Vaccinia Virus Ankara

Goonetilleke, Nilu; McShane, Helen; Hannan, Carolyn M.; Anderson, Richard; Brookes, Roger H.; Hill, Adrian V. S.

doi:10.4049/jimmunol.171.3.1602

Cited by 348 publications

(298 citation statements)

References 51 publications

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“…Running the ESAT-6 sequence through the SYFPEITHI database [29] predicted a 9-mer CD8 epitope restricted by H2-D b (residues 17-25; AIQGNVTSI). This peptide was recognized by the same frequency of IFN-c-producing CD8 cells as ESAT-6 [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] (data not shown). In addition, a CD4 epitope localized to residues 241-255 of Ag85B as well as a subdominant CD8 epitope located in residues 61-82 were found after vaccination with the adenovirus-based vaccine ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Both of these viruses have excellent safety profiles, and have already been widely used for vaccination purposes [14,15]. Both have recently been evaluated for TB vaccine delivery, and induced strong CD4 and CD8 responses [16,17] with protection against challenge with M. tuberculosis when administered by the mucosal route [17] or used to boost BCG [18].…”

Section: Introductionmentioning

confidence: 99%

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Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

et al. 2006

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To analyze the effect of vaccine delivery systems on antigen recognition and vaccine efficacy, we compared immune responses in mice immunized either with an adenovirus vector expressing a fusion of Ag85B and ESAT-6 or with the recombinant fusion protein in a liposomal adjuvant. Both vaccines induced high levels of antigen-specific IFN-c production. The adjuvanted protein vaccine induced primarily a CD4 T cell response directed to the epitope Ag85B 241-255 and gave efficient protection against subsequent Mycobacterium tuberculosis infection. In contrast, the adenoviral construct induced a strong CD8 response predominantly targeted to the epitope ESAT-6 15-29 and no significant protection against infection. Vaccination with the protein vaccine resulted in highly accelerated recall of Ag85B 241-255 -specific T cells immediately post M. tuberculosis challenge whereas the ESAT-6 15-29 epitope was barely recognized during infection. Delivery of the viral construct in cationic liposomes switched the immune response to a protective one dominated by CD4 T cells targeted to the Ag85B [241][242][243][244][245][246][247][248][249][250][251][252][253][254][255] epitope. These data demonstrate that the nature of the T cell response to a vaccine antigen is more important than its magnitude with respect to protective efficacy and that vaccine-mediated changes in immunodominance can result in T cell responses of limited relevance during the natural infection.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

et al. 2006

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“…Indeed, priming animals with BCG and then boosting with MVA expressing Ag85A (MVA-Ag85A) enhances survival and decreases bacterial burden after aerosol M. tuberculosis challenge compared to BCG alone [81,82]. MVA-Ag85A boosting of mice previously vaccinated with high doses of BCG enhanced CD4 + and CD8 + T cells responses to Ag85A peptides.…”

Section: Recombinant Vaccinia Virusmentioning

confidence: 99%

Next generation: tuberculosis vaccines that elicit protective CD8⁺T cells

Behar

Woodworth

2007

Expert Review of Vaccines

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SummaryTuberculosis continues to cause considerable human morbidity and mortality across the world, particularly in people coinfected with HIV. The emergence of multidrug resistance makes the medical treatment of tuberculosis even more difficult. Thus, the development of a tuberculosis vaccine is a global health priority. Here we review the data concerning the role of CD8 + T cells in immunity to tuberculosis and consider how CD8 + T cells can be elicited by vaccination. Many immunization strategies have the potential to elicit CD8 + T cells, and we critically review the data supporting a role for vaccine-induced CD8 + T cells in protective immunity. The synergy between CD4 + and CD8 + T cells suggests that a vaccine which elicits both T cell subsets has the best chance at preventing tuberculosis.

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“…T he generation and expansion of protective T cell responses are the goals of vaccines being developed to fight a variety of diseases including malaria, HIV, and tuberculosis (1)(2)(3). The usefulness of generating protective CD8 ϩ T cell responses has led to intense interest in understanding the cellular requirements for effective recall and boosting responses.…”

Section: Memory Cd8 ؉ T Cell Responses Expand When Antigen Presentatimentioning

confidence: 99%

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Cockburn

Chakravarty

Overstreet

et al. 2008

The Journal of Immunology

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Antimicrobial memory CD8+ T cell responses are not readily expanded by either repeated infections or immunizations. This is a major obstacle to the development of T cell vaccines. Prime-boost immunization with heterologous microbes sharing the same CD8+ epitope can induce a large expansion of the CD8+ response; however, different vectors vary greatly in their ability to boost for reasons that are poorly understood. To investigate how efficient memory T cell expansion can occur, we evaluated immune regulatory events and Ag presentation after secondary immunization with strong and weak boosting vectors. We found that dendritic cells were essential for T cell boosting and that Ag presentation by these cells was regulated by cognate memory CD8+ T cells. When weak boosting vectors were used for secondary immunization, pre-established CD8+ T cells were able to effectively curtail Ag presentation, resulting in limited CD8+ T cell expansion. In contrast, a strong boosting vector, vaccinia virus, induced highly efficient Ag presentation that overcame regulation by cognate T cells and induced large numbers of memory CD8+ T cells to expand. Thus, efficient targeting of Ag to dendritic cells in the face of cognate immunity is an important requirement for T cell expansion.

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Enhanced Immunogenicity and Protective Efficacy Against Mycobacterium tuberculosis of Bacille Calmette-Guérin Vaccine Using Mucosal Administration and Boosting with a Recombinant Modified Vaccinia Virus Ankara

Cited by 348 publications

References 51 publications

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

Next generation: tuberculosis vaccines that elicit protective CD8⁺T cells

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

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Enhanced Immunogenicity and Protective Efficacy Against Mycobacterium tuberculosis of Bacille Calmette-Guérin Vaccine Using Mucosal Administration and Boosting with a Recombinant Modified Vaccinia Virus Ankara

Cited by 348 publications

References 51 publications

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

Alteration of epitope recognition pattern in Ag85B and ESAT‐6 has a profound influence on vaccine‐induced protection against Mycobacterium tuberculosis

Next generation: tuberculosis vaccines that elicit protective CD8+T cells

Memory CD8+ T Cell Responses Expand When Antigen Presentation Overcomes T Cell Self-Regulation

Contact Info

Product

Resources

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Next generation: tuberculosis vaccines that elicit protective CD8⁺T cells