T cells induced by recombinant chimpanzee adenovirus alone and in prime-boost regimens decrease chimeric EcoHIV/NDK...

Area of Science:

• Vaccinology
• Immunology
• Viral Vector Technology

Background:

• Nonreplicating adenoviruses of chimpanzee origin (ChAdVs) are gaining popularity as vaccine vectors due to their safety and immunogenicity.
• Chimpanzee adenovirus serotype 68 (ChAdV-68) is a promising candidate for vaccine development.

Purpose of the Study:

• To genetically manipulate the ChAdV-68 genome for vaccine development.
• To evaluate the immunogenicity and efficacy of the ChAdV68.GagB vaccine in preclinical models.

Main Methods:

• Recloning of the ChAdV-68 genome using bacterial artificial chromosome recombineering.
• Generation of the ChAdV68.GagB vaccine by inserting HIV-1 Gag into the E1 region.
• Assessment of T-cell responses and viral load reduction in a mouse model.

Main Results:

• ChAdV68.GagB vaccine induced robust polyfunctional HIV-1-specific CD8(+) and CD4(+) T-cell responses with gut-homing phenotype.
• Vaccination with ChAdV68.GagB alone or in prime-boost regimens reduced surrogate virus load in mice.
• Protective effector memory responses were observed at peak and later time points.

Conclusions:

• ChAdV-vectored vaccines, specifically ChAdV68.GagB, demonstrate significant potential for HIV vaccine development.
• The vaccine elicits strong cellular immunity and provides protection against viral challenge in mice.
• Results support the continued development of ChAdV-based vaccines for human trials.