AriaVax's focus is on the delivery adjuvant for small molecule vaccine candidates. An adjuvant is a molecule or group of molecules that enhances the ability of the immunogen to elicit a robust immune response. Adjuvants largely enhance the magnitude, quality, time of onset and the duration of immune responses to co-administered immunogens. By covalently conjugating immunogens to aluminum oxide nanoparticles, the stability of the immunogen in mucosal environments such as the stomach will be enhanced beyond what is possible with any of the current vaccine technologies.
Although small molecules such as peptides generally require being conjugated to a carrier protein in order to elicit anti-peptide immune responses, there is a severe paucity of available carrier proteins that can be safely used. The aluminum oxide nanoparticle approach to enhance immune responses to small molecules addresses the issue of having a need for carrier proteins for the small molecules.
Helicobacter pylori (HP) is a Gram-negative, microaerophilic bacterium that can inhabit various areas of the stomach, particularly the antrum. HP causes chronic low-level inflammation of the stomach lining and is strongly linked to the development of duodenal and gastric ulcers and stomach cancer. HP is a major cause of diseases of the upper gastrointestinal tract. Eradication of the infection in individuals will improve symptoms including dyspepsia, gastritis and peptic ulcers, and may prevent gastric cancer. Rising antibiotic resistance increases the need for a prevention strategy for the bacteria.
An effective vaccine is needed to improve the success of anti-HP therapy. Cooperative action of cell-mediated, humoral and molecular responses is necessary for effective protection against it. Vaccines against HP can be used as prophylactic vaccines to prevent the infection or as therapeutic vaccines to cure the infection, to improve the eradication success of standard regimens or to reduce the bacterial density in the gastric mucosa and the risk for emergence of antibiotic resistant strains. There is no effective and safe vaccine against HP that is currently available for humans.
Human respiratory syncytial virus (RSV) is a virus that causes respiratory tract infections. It is the major cause of lower respiratory tract infections and hospital visits during infancy and childhood. A prophylactic medication (not a vaccine) exists for preterm birth (under 35 weeks gestation) infants and infants with a congenital heart defect (CHD) or bronchopulmonary dysplasia (BPD). Treatment is limited to supportive care, including oxygen therapy. In temperate climates there is an annual epidemic during the winter months. In tropical climates, infection is most common during the rainy season. In addition, elderly patients often suffer from RSV infections and complications from RSV infection may include pneumonia which could be fatal for immunocompromised individuals.
There is a conserved site in the envelope protein of HIV-1 gp120 that appears to be very important for HIV-1 to infect cells. However, preliminary data has indicated that individuals infected with HIV-1 do not make antibodies to this part of the envelope. We are in the process of developing peptides derived from this conserved domain in gp120 conjugated to Al2O3 nanoparticles as mucosal immunogens to determine if patients suffering from HIV-1 infection have improved prognoses compared with patients who do not have antibodies to this conserved site.
The original scientific publication describing the covalent conjugation of a peptide to aluminum oxide nanoparticles was produced in 1997 (Frei, A., Neutra, M.R. and Robey, F.A. Bioconjugate Chem. 8, 424-433 (1997)). This work describes in detail how to modify inexpensive aluminum oxide to attach organic molecules such as peptides. The size of the aluminum oxide was small enough so that it could be taken up by the immune system and antibodies could be produced against the attached peptide. Furthermore, the peptide-aluminum oxide nanoparticles conjugate could elicit an immune response when administered orally to mice, something that could not be observed when a commonly used adjuvant, alum, was tested with the same peptide.