Major Contracts Awarded for Anthrax, Malaria Vaccines
On 3 October, the US National Institute of Allergy and Infectious Diseases (NIAID) announced that it had awarded two contracts, totaling US$22.5 million, to spur the development of an improved anthrax vaccine. Contract recipients VaxGen (US) and Avecia (UK), will be charged with developing candidates from an experimental vaccine, called rPA102, that made by the US Army Medical Research Institute of Infectious Diseases (MD). This recombinant vaccine contains the anthrax “protective antigen” (which facilitates the entry of anthrax toxins into cells) and is based on the same technology as VaxGen’s gp120 AIDS vaccine. The contract calls for a product that protects against inhalation anthrax with no more than three immunizations; the current vaccine requires six vaccinations spread over 18 months. Both VaxGen and Avecia will submit a feasibility plan to manufacture, secure FDA approval and deliver up to 25 million doses of vaccine to the US government. VaxGen may base its manufacturing plan on use of the South San Francisco manufacturing plant now under construction as one production site for AIDSVAX.
NIAID also announced an award of up to $3.5 million over five years to Epimmune, Inc., for development of a malaria vaccine based on conserved cytotoxic and T helper cell epitopes. Epimmune is using a similar strategy to design an HIV vaccine that could provide cross-clade protection against disease.
Bavarian Nordic Announces Preliminary Data from HIV-MVA Therapeutic Vaccine Trial
A therapeutic vaccine containing HIV-nef in the MVA-BN vector (Modified Vaccinia Ankara-Bavarian Nordic strain) appears to be safe and immunogenic in HIV-infected people, according to Danish biotechnology company Bavarian Nordic, which released preliminary data in September 2002. Conducted at the University of Erlangen by Thomas Harrer, the Phase I/II trial enrolled 14 HIV-positive individuals (13/14 in chronic infection phase) who were on antiretroviral therapy for at least three months prior to the study and had undetectable viral loads and CD4 counts >400. Participants received three immunizations (weeks 0, 4 and 16) of 5 x 108 TCID50 of the vaccine.
Following the vaccinations, 11 of 14 volunteers showed increased numbers of Nef-specific T-cells. All participants maintained undetectable viral loads and showed an overall improvement in CD4 and CD8 T-cell counts. In an ongoing second phase of the study, HAART treatment was interrupted and volunteers are being followed, according to Barbara Petzold, Manager of Clinical Development. Treatment will be reinstated if viral load exceeds 5,000 at two consecutive timepoints (four weeks apart) or CD4 counts drop below 400. Plans call for testing the vaccine in HIV-negative volunteers next year.
Bavarian Nordic is also working with Epimmune (San Diego) on HIV vaccines containing epitopes (rather than whole genes), in a project comparing antigen delivery via DNA vaccines and MVA vectors. The epitopes were selected for their conservation across multiple HIV clades and the ability of several common HLA alleles (genes which play a key role in cellular immunity) to respond to them. Epimmune is currently testing a DNA vaccine prototype with 21 CTL epitopes in HIV-infected people and will soon begin Phase I studies in HIV-negative people, according to Mark Newman, Epimmune’s Vice President for Infectious Diseases. Later in 2003, Bavarian Nordic will test a “next-generation” candidate that also contains helper T-cell epitopes.
Bavarian Nordic is a leading player in MVA-based vectors, building on their MVA-BN platform technology derived from Anton Mayr’s MVA, which was extensively used in Germany as a smallpox “pre-vaccine” in the early 1970s The company is also developing MVA-BN as a potentially safer smallpox vaccine than the current one, which is dangerous for people with immune deficiencies (see interview with Philip Russell). Evidence that MVA-BN is safe even for HIV-infected people therefore has important implications beyond HIV therapeutics.
Remune in the News
On 26 September, the Thai subcommittee on HIV/AIDS Vaccine Development rejected an application from The Trinity Medical Group to extend a Phase II study of Remune, the whole-killed HIV immunogen developed by the California-based Immune Response Corporation. The request for a two-year extension to gather more information on the clinical effects of Remune used without anti-retroviral drugs, was denied on the grounds that the objectives had already been met by the previous study, said Dr. Prasert Thongcharoen, head of the vaccine subcommittee. Earlier this year, Trinity applied to the Thai FDA to have Remune licensed as a drug rather than a vaccine, but withdrew the application when approval appeared unlikely.
In Europe, Remune is moving towards a large-scale trial as a therapeutic vaccine used in conjunction with highly active antiretroviral therapy. In September, the Spanish Medication Agency (Agencia de Medicamento) submitted a written recommendation for a Phase III trial HAART-Remune trial to the European Agency for the Evaluation of Medicinal Products (EMEA). The recommendation drew on data from Eduardo Fernandez-Cruz (Gregario Maranon Hospital, Spain), some of which was presented at Barcelona (Abs. #ThOrA1482), showing that HIV-infected individuals treated with vaccine and HAART were 37% less likely to show viral loads exceeding 5,000 over a 30-month observation period than individuals receiving HAART alone.
Oral Vaccine Technology Licensed to UK Company for Non-HIV Vaccines
University of Maryland Biotechnology Institute (UMBI) licensed Bactofaction, a DNA delivery technology, to Microscience, a UK-based biotechnology company that recently launched an oral typhoid vaccine trial in the US. UMBI will retain the rights to develop HIV vaccines using the technology, which uses an attenuated Salmonella bacterial vector and allows for oral administration of DNA vaccines. The Institute of Human Virology at UMBI is collaborating with IAVI to move a vaccine based on this technology into clinical trials in Uganda and the US. Microscience will now be able to use Bactofaction in the development of orally-delivered vaccines for cancer and infectious diseases.