Nipah virus (NiV) and Hendra virus (HeV) are classified biological safety level 4 (BSL-4) viruses and are listed in Category C biothreat agents by the NIH and CDC. Nipah and henipaviral (HeV, NiV, Kumasi virus, KV, Cedar virus, CedV, Mojiang virus, MojV, and potentially new viruses in the genus) diseases are included in the 2018 annual review of the WHO Blueprint list of priority diseases. These emerging viruses, unlike other Category A biothreat viral agents such as Smallpox or Ebolavirus, can be isolated from natural reservoirs, grown in cell culture to high titers, and spread and amplified in livestock that are proven sources for transmission to humans, where subsequent person-to-person transmission facilities outbreaks. Transmission via aerosol and a high rate of lethality heighten their potential as biothreat agents. Currently, there is no approved human prophylaxis or therapeutic against NiV disease nor HeV disease. Vaccination may offer a viable strategy to provide significant public health benefit in endemic areas as well as provide an important component in our armamentarium to mitigate an outbreak of these viruses in the event they are used as a bioweapon. Horse anti-HeV vaccine (Equivac HeV), which subunit is genetically the same as the proposed human subunit vaccine, has been marketed by Zoetis in Australia since November 2012 under the authority of the Australian Pesticides and Veterinary Medicines Authority (APVMA) and is the first commercialized vaccine against any BLS-4 agent. The APVMA granted full registration of Equivac HeV in August 2015. Profectus BioSciences, Inc. is a vaccine focused company with experience of leading development processes through vaccine manufacturing, regulatory submissions, clinical trials and BLA application. For combating NiV and HeV diseases, the company has received a Partnership for Biodefense R01 award from NIAID for preclinical development of m102.4, an anti-NiV/HeV human MAb, as a post exposure therapeutic for NiV and HeV infection and a similar R01 to develop HeV-sG human vaccine in preclinical studies. Profectus has performed preclinical studies of HeV-sG subunit formulated with alhydrogel to be used in humans as a bivalent vaccine to prevent NiV or HeV infections or break their transmission. A Master Cell Bank (MCB) has been manufactured, GMP vaccine manufacturing process has been developed, toxicology vaccine lot has been produced, GLP tox study has been performed in rabbits, and efficacy after single dose immunization has been confirmed in African Green Monkeys (AGMs). Current formulation is liquid suspension, which although very efficient, is not very convenient for storage and transportation. Our objective here is to further develop the vaccine formulation through lyophilization, which is expected to dramatically improve the vaccine endurance to storage and transportation, also may allow a more convenient intranasal delivery. New more efficient adjuvants to enhance the durability of the immunity will be also explored. We plan to achieve these breakthrough improvements in the human vaccine stability, durability and efficacy through the following 5 Aims: 1) Lyophilization of Alum formulated HeV-sG ? nanoparticle formulation; 2) Testing alternate adjuvants for immunogenicity. Lyophilization of HeV-sG formulated with alternate adjuvant ? nanoparticle formulation; 3) Perform stability studies to support the animal efficacy studies; 4) Immunogenicity testing of reconstituted vaccine (IM) and nanoparticle formulation through intranasal delivery ? duration of immunity and efficacy in ferrets; and 5) Identification of a new product, choice of delivery ? intranasal or reconstituted IM, efficacy confirmation and duration of immunity in AGMs.
