The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc.

Xinle Cui

Clifford M Snapper

James J Mond

Provided are antigenic compositions and uses thereof that include at least two human herpesvirus (HHV) polypeptides involved in mediating HHV binding, fusion, and entry into host cells, such as gp350, gH, gL, and gB, or nucleic acids encoding the polypeptides. The two HHV polypeptides comprise any combination of: a gB polypeptide; a gp350 polypeptide; a gL polypeptide; and a gH polypeptide, and optionally any one or more of the following polypeptides: gp42, gM, gN, gl, gC, gE, gD, ORF68, BMRF-2, BDLF2, UL128, UL130, UL131A, and gpK8.1. Also disclosed are methods of inducing an immune response or treating or preventing an HHV infection in a subject by administering to the subject at least two of the HHV polypeptides or nucleic acid(s) encoding the same. Methods of passively transferring immunity using high-titer anti-HHV antibodies or immune cells are also disclosed.

Vaccine compositions of herpesvirus envelope protein combinations to induce immune response

The present disclosure provides fusion proteins that incorporate unique mechanisms for multimerizing antigens to enhance their immunogenicity. The fusion proteins comprise at least two antigens, or other vaccine related proteins, separated by a linker sequence and an oligomerization domain. When expressed, the fusion protein forms a muKimeric protein complex, This approach can be used to muHimeri?.e a single antigen/protein or to create multimers comprising two or more different antigens/proteins. Also provided are nucleic acids encoding the fusion proteins. Yet another aspect is directed to methods of inducing or suppressing an immune response in a subject by administering to the subject a vaccine composition comprising a fusion protein or nucleic acid encoding the fusion protein, optionally without using an adjuvant.

Multimeric fusion protein vaccine and immunotherapeutic

The present disclosure provides fusion proteins that incorporate unique mechanisms for multimerizmg antigens to enhance their immunogenicity. The fusion proteins comprise at least two antigens, or other vaccine related proteins, separated by a linker sequence and an oligomerization domain. When expressed, the fusion protein forms a muKimeric protein complex, This approach can be used to muHimeri?.e a single antigen/protein or to create multimers comprising two or more different antigens/proteins. Also provided are nucleic acids encoding the fusion proteins, Yet another aspect is directed to methods of inducing or suppressing an immune response in a subject by administering to the subject a vaccine composition comprising a fusion protein or nucleic acid encoding the fusion protein, optionally without using an adjuvant.

The present disclosure provides modified human herpesvirus glycoprotein B (gB) proteins that incorporate unique mechanisms for generating proteins that mimic their native conformation to enhance their immunogenicity. The modified herpesvirus gB proteins insert a peptide linker at the furin cleavage site in the extracellular domain of herpesvirus gB. When expressed, the gB subunit associates in triplicate to produce a homotrimeric complex, mimicking the native conformation of the gB protein. Also provided are protein complexes comprising a homotrimeric complex of a modified herpesvirus gB protein and herpesvirus gH and gL proteins. Also provided are nucleic acids encoding the modified herpesvirus gB proteins, methods of inducing or suppressing an immune response in a subject by administering a vaccine comprising the modified herpesvirus gB protein, or nucleic acid encoding the same, or a protein complex comprising a homotrimeric complex of the modified herpesvirus gB protein and herpesvirus gH and gL proteins.

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Gaithersburg, MD, United States of America

Xinle Cui