Assessment of Unwanted Immunogenicity
Unwanted immunogenicity can often result in projects being cancelled or severely delayed, to the substantial cost of the developer, and so ensuring this particular process goes smoothly is at the forefront of industry leaders' minds.
One organisation which has recently successfully navigated this stage is Medicago, a biotechnology company which develops vaccines based on proprietary manufacturing technologies and virus-like particles.
The company announced that it has received US Food and Drug Administration (FDA) clearance for its phase I H1N1 influenza VLP vaccine candidate clinical trial in the US, which the firm plans to initiate in the coming weeks.
This will eventually lead into Medicago's US phase IIa trial for its seasonal trivalent vaccine with the recommended H1N1, H3N2 and B influenza strains, which will take place later this year.
According to Andy Sheldon, president and chief executive of Medicago, securing the approval of the FDA is a "significant milestone" in the advancement of the company's seasonal influenza vaccine.
"Our recent positive phase II interim results for our avian influenza vaccine have demonstrated to date the safety and immunogenicity of our vaccine manufacturing platform and provide us with solid support for the development of our seasonal vaccine candidate.
"In addition, our ability to rapidly and cost-effectively produce quality vaccines is a key advantage over traditional methods and will allow us to participate in the $2.8 billion (£1.7 billion) seasonal market which is expected to grow to $6.3 billion by 2019," he explained.
Sheldon said that the phase I, randomised, double-blind, multicentre, active- and placebo-controlled dose-ranging study will help to evaluate the "safety, tolerability and immunogenicity" of a single non-adjuvanted dose of the H1N1 vaccine in 100 study participants aged between 18 and 49.
Each of the subjects will either receive an injection of the placebo, Medicago's H1N1 vaccine or an H1N1 vaccine from a licensed trivalent vaccine, with primary safety and immunogenicity results expected within three months.
The chief executive said that 2011 will be an "eventful year" for the company, as it plans to complete a phase II trial for its H5N1 vaccine and a US phase I trial for the H1N1 vaccine, as well as starting a US phase IIa trial for a seasonal vaccine.
"We will also have a fully operational US commercial-grade vaccine production facility which will have the capacity to produce more than 40 million seasonal vaccine doses per year," Sheldon added.
Another company with high hopes for a product and confident of its immunogenicity is Bavarian Nordic A/S, a Denmark-based biotechnology company, which has developed a novel smallpox vaccine.
According to the firm, the highly attenuated, non-replicating smallpox vaccine showed excellent safety and immunogenicity in atopic dermatitis patients in a phase II clinical trial recently.
Known as Imvamune, it is derived from the parent strain Modified Vaccinia virus Ankara (MVA-BN), which has lost the capacity to replicate in human cells.
The phase II trial included 350 subjects aged between 18 and 40 years who suffered from mild to moderate atopic dermatitis, and 282 healthy patients, who all received two vaccinations four weeks apart.
According to Dr. Maria Yadira Hurley, a dermatologist at St Louis University, the vaccine was well tolerated, with no cases of eczema vaccinatum, myocarditis or pericarditis, while existing symptoms did not worsen.
Based upon these high results and over a dozen other clinical trials including 2,500 subjects, the US government is now stockpiling the vaccine.
"These results strongly suggest that [it] may be suitable for vaccination of atopic dermatitis patients, who are excluded from vaccination with traditional smallpox vaccines," Dr. Hurley told the American Academy of Dermatology.