Nasal vaccine for smallpox protects animals against 77 times the potentially lethal dose of smallpox

Scientists at NanoBio Corporation and the University of Michigan have demonstrated their nasally delivered vaccinia vaccine can protect animals against 77 times the potentially lethal dose of smallpox, and without the safety risks of current vaccines for smallpox.

Vaccinia virus is related to smallpox virus and builds immunity against it.

The new vaccine confers a high level of safety because it contains inactivated vaccinia virus, not the live virus contained in current smallpox vaccines, according to the scientists. Live viruses can elicit adverse reactions; yet previous attempts to use inactivated virus have failed to rouse an adequate immune response against smallpox, the scientists said.

The current study in mice demonstrates that NanoBio's killed-virus vaccine elicits a robust immune response because it delivers immune-alerting antigens directly to the lining of the nasal mucosa, where the virus first enters the body. Immune cells inside the nose immediately recognize the foreign invader and quickly build an immune response against it, a process known as "mucosal" immunity.

Mucosal immunity provides a critical first response against respiratory viruses, yet injected vaccines do not induce mucosal immunity, said James R. Baker Jr., M.D. founder and chairman of NanoBio Corporation. NanoBio is a spin-off from the University of Michigan.

"The key finding is that we have validated in animals a new means of immunization that produces a unique and highly effective immune response without the potential risks of smallpox vaccination that are no longer considered acceptable in the population at large," said Baker.

"The safety and speed of our nasally delivered vaccine would provide the necessary protection to the public in the event of a bioterrorist attack or a natural outbreak of a related orthopoxvirus infection such as monkeypox," he said.

Results of the study are published in the February 2008 issue of Clinical and Vaccine Immunology. The study is the first to demonstrate protective immunity against smallpox using a vaccine with inactivated virus, said Baker.

The data are the latest in a series of preclinical vaccine studies that validate NanoBio's patented nanoemulsion platform, a suspension of oil, water, alcohol and antimicrobial surfactant together with antigens from specific pathogens. The nasally delivered vaccines easily penetrate mucous membranes, where dendritic cells engulf the antigen and immediately present it to the immune system.

This rapid awakening of the immune system via mucous membranes negates the need for inflammatory stimulants used in traditional injected vaccines, which can cause pain and swelling at the site of vaccination, said Baker.

Animal studies indicate that NanoBio's vaccines quickly trigger robust immunity -- without adverse effects -- against a wide array of viruses and bacteria, including influenza, hepatitis B, RSV, anthrax and HIV.

A study to be published this month in the journal AIDS Research and Human Retroviruses demonstrates that their HIV vaccine produces both mucosal immunity as well as systemic immunity -- the immune system's long-term memory that enables it to recognize and combat future infections.

Both types of immunity are critically important, but developing mucosal immunity is particularly valuable in combating sexually transmitted diseases because they enter the body through mucous membranes, added Baker. Vaccines that are delivered to one mucosal surface, such as inside the nose, build immunity at distant mucosal surfaces as well.

"When you present an infection on one mucosal surface, the immune cells that are recruited at that surface also traffic throughout all the mucosal surfaces," Baker said. "Our HIV study suggests that the nanoemulsion should be evaluated as a mucosal adjuvant for multivalent HIV vaccines."

Both the HIV and vaccinia vaccine studies demonstrate that vaccinated animals developed mucosal and systemic immunity as well as cellular immunity, whereby specific immune cells (CD8 and CD4 T cells) were successfully primed to recognize and destroy infected cells in the body.

Cellular immunity kills infected cells in the body and essentially removes the infection machinery of the virus. Previous HIV vaccines have focused on inducing cellular immunity but not mucosal immunity, said Baker. The more types of immunity generated by a vaccine, the higher the level of protection and infection-fighting capability the vaccine can provide.

NanoBio is in various stages of testing its pipeline of nasally delivered vaccines. Human testing of the influenza and hepatitis B vaccines are being planned, and data from ferret studies on the influenza vaccine are expected this quarter.

About NanoBio

NanoBio(R) Corporation is a privately held biopharmaceutical company focused on developing and commercializing anti-infective products and mucosal vaccines derived from its patented NanoStat(TM) technology platform. The company's lead product candidates are topical treatments for herpes labialis (cold sores), onychomycosis (nail fungus), MRSA and mucosal vaccines for influenza and hepatitis B. The company's headquarters and laboratory facilities are located in Ann Arbor, Mich.