Evaluation of Adenovirus recombinants displaying a cross-protective HPV16 L2 epitope in mice.

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

Convergence of a common solution to broad ebolavirus neutralization by glycan cap directed human antibodies

Antibodies that target the glycan cap epitope on ebolavirus glycoprotein (GP) are common in the adaptive response of survivors. A subset is known to be broadly neutralizing, but the details of their epitopes and basis for neutralization is not well-understood. Here we present cryo-electron microscopy (cryo-EM) structures of several glycan cap antibodies that variably synergize with GP base-binding antibodies. These structures describe a conserved site of vulnerability that anchors the mucin-like domains (MLD) to the glycan cap, which we name the MLD-anchor and cradle. Antibodies that bind to the MLD-cradle share common features, including the use of IGHV1-69 and IGHJ6 germline genes, which exploit hydrophobic residues and form beta-hairpin structures to mimic the MLD-anchor, disrupt MLD attachment, destabilize GP quaternary structure and block cleavage events required for receptor binding. Our results collectively provide a molecular basis for ebolavirus neutralization by broadly reactive glycan cap antibodies

Evaluation of Adenovirus recombinants displaying a cross-protective HPV16 L2 epitope in mice.

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