Vaxfectin-formulated H5N1 pandemic influenza achieves T-cell responses and cross-clade reactivity in humans

Vical Incorporated has announced that the company's Vaxfectin-formulated H5N1 pandemic influenza DNA vaccines induced T-cell responses against a matching strain of influenza virus and demonstrated cross-clade antibody responses against a different strain in a Phase 1 clinical trial.

The company previously reported that the vaccines had achieved potentially protective levels of antibody responses in up to 67% of evaluable subjects in the trial's higher dose cohorts. Vical researchers presented the expanded data, as well as new nonclinical data from the company's RapidResponse DNA vaccine manufacturing program, this week at the DNA Vaccines 2008 Conference (Las Vegas - December 9-11).

H5N1 Pandemic Influenza Vaccine Phase 1 Trial Update

New data presented at the conference indicates that the company's monovalent Vaxfectin-formulated H5N1 pandemic influenza DNA vaccine induced T-cell responses against the H5 antigen in 75% to 100% of evaluable subjects in the various cohorts. T-cell responses could be important in protecting against serious disease and in limiting the spread of disease during an outbreak.

The monovalent vaccine, which was based on the H5N1 influenza virus strain, A/Vietnam/1203/04, also induced antibody responses against the H5N1 influenza virus strain, A/Hong Kong/156/97 from a different clade, in 50% of responders. Cross-clade responses could be important in providing protection against emerging strains of influenza before a matching vaccine could be deployed.

Antibody and/or T-cell responses against the matching H5 antigen and the conserved NP and M2 antigens were detected in a majority of subjects receiving the trivalent vaccine. Responses against conserved antigens could provide protection against serious disease or death during an outbreak of a new strain of influenza for which a vaccine had not yet been developed.

Vical had previously reported that the monovalent vaccine achieved potentially protective levels of antibody responses (H5 hemagglutination inhibition, or HI, titers of at least 40 and at least a four-fold increase from baseline) in at least 50% and up to 67% of evaluable subjects in a 100-subject Phase 1 trial. In the two monovalent vaccine cohorts receiving the highest H5 DNA dose (1 mg), 80% to 100% of the responders had sustained responses through Day 182.

Vical's monovalent vaccine contained a plasmid (a closed loop of DNA) encoding the hemagglutinin (HA) surface protein from the H5N1 influenza virus strain, A/Vietnam/1203/04. It was designed primarily to elicit antibody responses against the H5 protein but could elicit T-cell responses against H5 as well. Vical's trivalent vaccine contains the H5 plasmid plus separate plasmids encoding consensus sequences of two highly conserved influenza virus proteins: nucleoprotein (NP) and ion channel protein (M2). The trivalent vaccine was designed to elicit a combination of T-cell and antibody responses against all three proteins. Both vaccines were formulated with the company's Vaxfectin adjuvant, which has demonstrated effectiveness with a variety of DNA vaccines in multiple animal models as well as dose-sparing and immune-enhancing ability in animals with a conventional seasonal influenza vaccine.

RapidResponse DNA Vaccine Manufacturing Update

New data presented at the current conference indicates that a single injection of a Vaxfectin-formulated influenza vaccine produced by the company's RapidResponse manufacturing system provided complete protection of mice against challenge with highly lethal doses of H3N2 influenza virus. A dose response was apparent, as mice vaccinated with decreasing doses below a threshold level were afforded decreasing protection. The ratio of Vaxfectin adjuvant to DNA in the vaccine also affected the protective efficacy of the vaccine. In separate tests, the use of alternative PCR primers, an integral part of the RapidResponse manufacturing process, did not significantly affect the protective efficacy of the resulting product.

The RapidResponse system is designed to allow extremely rapid and large-scale production of DNA vaccines with low capital requirements. The company is proceeding with the development of the RapidResponse platform under the second year of grant funding awarded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH).