Safety and Immunogenicity of Adenovirus and Poxvirus Vectored Vaccines against a Mycobacterium Avium Complex Subspecies

Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as a booster vaccine following a simian adenovirus (ChAdOx2) prime. We demonstrate that a heterologous prime-boost schedule is well tolerated and induced T-cell immune responses.

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T-cell immune responses in Mycobacterium avium-infected mice.

Infection and Immunity ◽

10.1128/iai.60.1.150-153.1992 ◽

1992 ◽

Vol 60 (1) ◽

pp. 150-153 ◽

Cited By ~ 21

Author(s):

R D Hubbard ◽

C M Flory ◽

F M Collins

Keyword(s):

T Cell ◽

Immune Responses ◽

Mycobacterium Avium ◽

T Cell Immune Responses

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Safety and Immunogenicity of a Novel Recombinant Simian Adenovirus ChAdOx2 as a Vectored Vaccine

Vaccines ◽

10.3390/vaccines7020040 ◽

2019 ◽

Vol 7 (2) ◽

pp. 40 ◽

Cited By ~ 7

Author(s):

Pedro M. Folegatti ◽

Duncan Bellamy ◽

Rachel Roberts ◽

Jonathan Powlson ◽

Nick J. Edwards ◽

...

Keyword(s):

Immune Responses ◽

Mycobacterium Avium Subspecies Paratuberculosis ◽

Intracellular Pathogens ◽

Neutralising Antibodies ◽

Dose Escalation Study ◽

Cellular Immune Responses ◽

Simian Adenovirus ◽

Adenovirus Vectors ◽

Vectored Vaccine ◽

Cellular Immune

Adenovirus vectored vaccines are a highly effective strategy to induce cellular immune responses which are particularly effective against intracellular pathogens. Recombinant simian adenovirus vectors were developed to circumvent the limitations imposed by the use of human adenoviruses due to widespread seroprevalence of neutralising antibodies. We have constructed a replication deficient simian adenovirus-vectored vaccine (ChAdOx2) expressing 4 genes from the Mycobacterium avium subspecies paratuberculosis (AhpC, Gsd, p12 and mpa). Safety and T-cell immunogenicity results of the first clinical use of the ChAdOx2 vector are presented here. The trial was conducted using a ‘three-plus-three’ dose escalation study design. We demonstrate the vaccine is safe, well tolerated and immunogenic.

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Aryloxy Triester Phosphonamidates of Phosphoantigens Exhibit Favorable Stability and Potent Activation of Vγ9/Vδ2 T‐Cells

10.26434/chemrxiv.6755033.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Hachemi Kadri ◽

Taher E. Taher ◽

Qin Xu ◽

Richard T. Bryan ◽

Benjamin E. Willcox ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Immune Responses ◽

Serum Stability ◽

T Cell Immune Responses ◽

Further Development

We previously reported the application of the aryloxy triester phosphoramidate prodrug technology to the phosphoantigen (E)-4-hydroxybut-2-enyl phosphate (HMBP). Although these prodrugs exhibited potent activation of Vγ9/Vδ2 T‐cell immune responses, their stability was low due to the rapid cleavage of the -O-P- bond. To address this, we herein report the application of the same prodrug strategy to two HMBP phosphonates, which have stable -CH2-P- or -CF2-P- bonds. These HMBP phosphonate prodrugs, phosphonamidates, exhibited excellent serum stability and potent activation of Vgama9/Vdelta2 T‐cells making them attractive compounds for further development as potential immunotherapeutics.

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