Ramping Up Flu Vaccine Efforts 학부 4학년 류광렬, 김혜원

Replikins-Based Approach Replikins are a group of peptides, whose increase in concentration in virus or other organism proteins is associated with rapid replication. It is often measured in number of replikins per 100 amino acids. This particular group of peptides have been found to play a significant role in predicting both infectivity and lethality of various viral strains. In particular, this group allowed the prediction of the A/H1N1 pandemic almost one year before onset

virus-like particle-based (VLP) Novavax plans to create a virus-like particle-based (VLP) vaccine against the H1N1 strain The VLPs contain the proteins that make the virus’ outer shell and the surface proteins, without the RNA required for replication. “There’s no genetic material in these VLPs, and they are unable to replicate,”

H1N1 Influenza A (H1N1) virus is a subtype of influenzavirus A and the most common cause of influenza (flu) in humans. Some strains of H1N1 are endemic in humans and cause a small fraction of all influenza-like illness and a large fraction of all seasonal influenza. H1N1 strains caused roughly half of all human flu infections in 2006. Other strains of H1N1 are endemic in pigs and in birds. In June 2009, World Health Organization declared that flu due to a new strain of swine-origin H1N1 was responsible for the 2009 flu pandemic. This strain is often called "swine flu" by the public media.

Robust Response Medicago received the genetic sequence for the H1N1 influenza virus strain in late April to begin testing using its virus-like particle technology The goal is to prove the safety of a vaccine produced using Medicago’s plant-based technology

Medicago’s VLP technology has the potential to produce pandemic vaccines before a pandemic strikes and will be in a position to supply large volumes of vaccines to the global market once human trials are completed. In preclinical trials, the vaccine conferred cross protection against several strains of the H5N1 influenza virus, including those from Indonesia, Vietnam, China, and Turkey. “We also are developing a seasonal vaccine to follow our H5N1 vaccine candidate.”

Flagellin-Based Approach VaxInnate is developing an H1N1 flagellin-based vaccine for swine flu. The flagellin stimulates the immune cells in the body to release cytokine and immune-mediator molecules that initiate an immune response. VaxInnate uses HA and M2 proteins to stimulate an immune response to influenza virus. HA mutates rapidly, but the M2ectodomain (M2e) has remained virtually unchanged during the past century and across influenza A strains. “The body doesn’t recognize this as immunogenic,” Dr. Taylor says, until it is fused to flagellin

M2e and HA each can be produced in bacterial expression systems, shortening development time. Dosage is one-tenth that required from egg-based vaccines, so “we can make tens of thousands of doses per liter of bacteria.” And, for a seasonal vaccine, he suggests VaxInnate can include four viral strains rather than the usual three.

Nanoemulsion-Antigen Mixture NanoBio’s NanoStat™ vaccine platform mixes an antigen from an influenza strain with a proprietary nanoemulsion. When administered in the nose, the vaccine “coats the mucosa” and then is taken up by dendritic cells that deliver the antigen to the lymph nodes, thymus, and spleen, triggering an immune response The dendritic cells are specific for wanting to engulf lipids, so they take up the nanoemulsion-antigen mixture more efficiently than other vaccines

In one day, 100 million doses of the emulsion can be made. It’s very stable and has remained viable for more than three years. Once the nanoemulsion is made, it can be stored so different antigens can be mixed into the nanoemulsion as needed, making it easier to respond to emerging needs. The vaccine also is being investigated for hepatitis B, Haemophilus influenzae type B, RSV, cancer, anthrax, smallpox, and other diseases. Using the same technology platform, NanoBio is also developing a nasal spray that kills on contact any strain of influenza by attacking the lipid envelope that surrounds the virus.

Minimizing Adjuvant Vaxart is developing oral vaccines for seasonal and pandemic influenzas based upon a nonreplicating adenovirus 5 vector that expresses both a target antigen such as HA and a piece of double-stranded RNA that acts as an adjuvant via the toll-like receptor 3. Presenting the adjuvant and antigen together to the immune system at the cellular level minimizes the amount of adjuvant needed to get a strong immune response to the target antigen. Unlike most vector approaches, performance is unaffected by previous exposure

In preclinical trials, the avian flu vaccine showed a strong immunologic response, even against mismatched strains, suggesting it may remain effective as viruses mutate. To combat the current H1N1 flu strain, a synthesized HA gene with the matching sequence is being used to produce a vaccine without growing the flu virus itself Because the vaccine is oral, it could be delivered by the postal service and administered by patients themselves.