Clinical Stage HIV Vaccine Candidate and Other Vaccine Vectors

Summary Replication-defective viruses integrate the safety advantages of a killed virus vaccine and the immunogenicity of a live virus vaccine. Professor David Knipe and his research team present a novel replication-defective HSV-1 virus for the delivery of heterologous immunogens and nucleic acids relevant to vaccine applications. Viral replication is inhibited through the mutation of multiple early immediate genes of the HSV-1 virus, including ICP27 and ICP8. The mutation of multiple genes (e.g. 4 early immediate genes) interrupts a tightly regulated genetic cascade that is responsible for late genetic transcription in the HSV-1 replication cycle, generating a replication defective vaccine vector of high anticipated safety.

Advantages of the platform include broad infectivity across a range of host cells (including mucosal membranes), rapid T-cell responses, activation of the innate immune response through toll-like receptors (TLR-2 and TLR-9), the ability to accommodate large heterologous DNA insertions at multiple loci (at least as large as 10 kb), and the ability to generate a durable immune response. In addition, complementary cell-lines have been developed capable of propagating the replication-defective HSV-1 mutants. Preexisting cell lines will enable rapid development cGMP-compliant strains and enable high-titer production of vaccine vectors for manufacturing.

Licensable opportunities for the viral platform exist in the areas of HIV, West Nile virus, SARS, anthrax, and influenza. Administration of HSV vaccine vectors, containing multiple proteins of the simian immunodeficiency virus (SIV), has led to impressive protection of macaques against SIV challenge, based on a combined antibody and T-cell response. As a promising vaccine approach for AIDS, this has led to significantly lower viral loads in treated macaques at peak challenge, 12-weeks post challenge, and even after 24 weeks in certain macaques. Significant clinical development of the HIV vaccine is anticipated in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID).

Applications A new vaccine platform is presented along with significant vaccine candidates spanning HIV, West Nile virus, SARS and anthrax. In addition to these vaccine vectors, which have been generated in the Knipe laboratory and have elicited promising immune responses in mice, future pipeline candidates may address hepatitis C, which is expected to have an analogous vaccine construct to West Nile virus. The Knipe lab is also currently developing a vaccine construct for avian flu by targeting H5 hemagglutinin and other key avian flu genes, thus leading to a multiplexed approach.

Partnership Opportunity Harvard seeks an industrial partner to develop the various vaccine applications, with a specific focus on a clinical stage HIV vaccine candidate. The opportunity may be particularly attractive for a company seeking to acquire a new vaccine vector platform consisting of a series of vaccine candidates. In conjunction with strong IP, commercialization efforts may leverage the lab’s significant expertise in HSV vaccine vectors, as well as proprietary materials including vaccine vector constructs and complementary cell lines for vaccine vector production.



IP Status Harvard has filed patent applications in all relevant markets covering compositions of HSV replication-defective viruses. In the context of replication-defective HSV-1 vaccines, Harvard’s significant patent estate includes specific mutations to early immediate genes; insertion of heterologous immunogens/nucleic acids; and compositions of relevant cell lines for recombinant vaccine vector production.

Publications Murphy et al., Vaccine protection against simian immunodeficiency virus by recombinant strains of herpes simplex virus, Journal of Virology, 73(17), 7745-7754, 2000. For Further Information Please Contact the Director of Business Development Maryanne Fenerjian Email: [email protected] Telephone: (617) 432-0920

Inventor(s): Knipe, David M.

Type of Offer: Licensing



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