Breadth of T Cell Responses After Immunization with Adenovirus Vectors Encoding Ancestral Antigens or Polyvalent...

Area of Science:

• Immunology
• Virology
• Vaccinology

Background:

• Oncogenic human papillomaviruses (HPVs) are typically cleared by T cell-mediated immunity.
• HPVs belong to an ancient and diverse virus family, necessitating strategies for broad immune response induction.

Purpose of the Study:

• To evaluate the potential and limitations of inducing cross-reactive T cells or using polyvalent vaccines against oncogenic HPVs.
• To assess the sequence identity threshold for effective T cell responses against diverse HPV strains.

Main Methods:

• Designed ancestral and circulating PV sequences based on conserved E1 and E2 protein domains.
• Utilized a recombinant adenoviral vector encoding PV sequences fused to a murine invariant chain adjuvant.
• Administered vaccines to naïve mice and measured CD8+ T cell responses against peptide pools representing HPV strains and an ancestral PV.

Main Results:

• An ancestral vaccine antigen needed approximately 90% sequence identity to circulating PVs to avoid a significant drop (~90%) in CD8+ T cell responses.
• Combining two or three type-specific PV vaccines did not substantially decrease CD8+ T cell responses to individual targets.
• Polyvalent HPV vaccines based on E1/E2 proteins could elicit responses against multiple PV types.

Conclusions:

• The cross-reactivity of ancestral vaccines appears insufficient given the sequence diversity among HPV types.
• Polyvalent HPV vaccines show potential for broader protection by targeting multiple HPV types.
• Vaccine design must consider sequence conservation thresholds for effective T cell-mediated immunity against diverse HPV strains.