Evaluation of Adenovirus recombinants displaying a cross-protective HPV16 L2 epitope in mice.
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Date
2013-11-07
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Johns Hopkins University
Abstract
HPV minor capsid protein L2 has been shown to induce cross-protective and cross-neutralizing antibodies against diverse HPV types, but at a low titer. Adenovirus "capsid display" has the potential to enhance the immunogenicity of heterologous B cell epitopes, and recombinants were engineered to display an HPV L2 epitope on the surface hyper variable regions (HVR) 1 or 5 of adenovirus capsid protein hexon. Mice were immunized by subcutaneous injection with L2-recombinant adenovirus particles with or without adjuvant (a mixture of Aluminum hydroxide and monophosphoryl lipid A {MPL}). ELISA assays of the serum from immunized mice shows that these recombinants induced anti-L2 antibodies as well as anti-adenovirus antibodies. The immunized mice were challenged with HPV pseudovirus (PsV) encapsidating a luciferase reporter, first with HPV16 pseudovirus and then heterologously with HPV56 pseudovirus. The data show that mice were protected against high dose infection with HPV16; however there was no protection in the heterologous challenge with HPV56. The data demonstrate that adenovirus capsid display recombinants are capable of inducing protective immunity against HPV16 but do not cross protect against HPV56.
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Keywords
HPV16 L2, adenovirus recombinants, capsid display