Live Attenuated Influenza Vaccine (LAIV)

LAIV is a novel intranasal live attenuated influenza vaccine being developed to prevent infection from seasonal and pandemic influenza.

BioDiem has exclusive rights from the Institute of Experimental Medicine (IEM) in St. Petersburg to commercialize the LAIV technology outside Russia and the Commonwealth of Independent States.  The vaccine has over ten years of safe and effective use there, where over 80 million doses have been distributed.  LAIV is a novel influenza vaccine delivered by nasal spray and is based on the live attenuated influenza vaccine developed at the IEM. 

Unlike the more traditional influenza vaccinations which are injectible, the LAIV nasal spray influenza vaccine does contain live viruses. However, the viruses are attenuated (weakened) and cannot cause illness. The weakened viruses are cold-adapted, which means they are designed to only cause infection at the cooler temperatures found within the nose. The viruses cannot infect the lungs or other areas where warmer temperatures exist.

Advantages of the LAIV system are that it can be manufactured in either cell culture or traditional egg based culture. Cell culture production is more reliable which is important in the event of an epidemic or pandemic. In addition, intranasal delivery offers several benefits such as ease of use. The vaccine is delivered to the optimal site for the immune system in terms of antibody and cell mediated immunity and mimics the natural route of infection.

Through the IEM, BioDiem continues to develop new vaccine strains using classical genetic re-assortment methodologies. Reassortants, from which the LAIV is made, are virus strains originated by the exchange of one or more genome segments between two or more different influenza viruses as a consequence of mixed infection.  The genome segments are taken from live, cold-adapted, attenuated donor influenza strains.

LAIV Development Status

BioDiem licensed world manufacturing rights to European vaccine company Nobilon International B.V., a subsidiary company of Schering-Plough (recently acquired by Merck), and marketing rights throughout the world except North America in 2004.  Nobilon can exercise an option to acquire marketing rights for North America subject to certain terms.  Japanese manufacturing, sales and marketing rights are owned by BioDiem.

SEASONAL INFLUENZA VACCINE

Nobilon is responsible for developing the influenza vaccine registration in Europe, using cell-culture manufacturing techniques.  A Phase I clinical trial was successfully completed in 2009 and a Phase II clinical trial is underway in the Northern Hemisphere.   

PANDEMIC INFLUENZA VACCINE

The clinical assessment of pandemic variants continues at the Institute of Experimental Medicine (IEM) in Russia. BioDiem has several agreements in place concerning the development of pandemic influenza vaccines. These include agreements with not-for-profit organisations such as the World Health Organisation (WHO).

H1N1 

As part of the World Health Organization’s Global Pandemic Influenza Action Plan to Increase Vaccine Supply in developing countries, BioDiem and Nobilon have agreed to allow the IEM to supply the WHO with live attenuated influenza vaccine (LAIV) reassortants.  Together with know-how supplied by Nobilon, these will be sub-licenced by the WHO to private companies or governmental or non-governmental organizations for the public sector in developing countries.  This will enable sub-licencees to produce the vaccine in eggs and to distribute seasonal and pandemic vaccines.  Sub-licences have been granted to the Government Pharmaceutical Office of Thailand, the Serum Institute of India Ltd and Zhejiang Tiayuan Biopharmaceuticals of China. Sales to the private market, of these developing countries may trigger royalty payments to BioDiem.

Phase II clinical trials have commenced in Russia and are expected soon to commence in Thailand and India

H5N2 Strain

The IEM successfully completed a Phase II trial using an H5N2 reassortant in 2008. The trial demonstrated that the vaccine was safe, effective and lowly reactogenic, with no fever reactions. This vaccine is already registered in Russia and has been made available to the WHO to support early registration of pandemic vaccines in developing countries. 

H5N1 & H7N3 Strains

BioDiem and Nobilon have a Co-operative Research and Development Agreement (CRADA) with the Centers for Disease Control and Prevention to develop an H5N1 candidate vaccine in cell culture against the H5N1 avian influenza strain. Part of this research is assessing the benefits of an LAIV vaccine compared to an inactive influenza vaccine. Currently this project is at the pre-clinical stage with results expected in 2010 from an animal study assessing infectivity, immunogenicity and protective efficacy.

The Institute of Experimental Medicine also has a collaboration agreement with PATH Vaccine Solutions (PVS).  The agreement is to support the development by the IEM of a prototype pandemic live, attenuated influenza vaccine for use in developing countries. The aim of the agreement is to demonstrate that the cold–adapted master virus bearing avian or human influenza virus genes from viruses with pandemic potential will be safe and produce an immune response in humans and to carry out pre-clinical and clinical trials, with the ultimate goal of a Phase I trial expected to begin in late 2011.  Data and patents arising from the development plan will be available for use in developing countries under the WHO’s Global Pandemic Influenza Action Plan and for use by Nobilon/Merck elsewhere.