New methods and platforms for rapid development and production of effective subunit vaccines have become a 21st-century imperative. Not only is it important to rapidly express and produce a large number of antigens, but those antigens must be expressed and folded such that their effectiveness in preclinical studies is predictive of their potential effectiveness as vaccines. This task has created a bottleneck in vaccine development because recombinant protein expression is difficult and time-consuming, involving a large number of variables. Highly developed bacterial expression platforms are particularly suited to overcoming many obstacles because of rapid growth rates and a large number of expression tools that have been developed to meet these challenges (
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).
Deciding which tools or combinations of tools will be effective in producing a particular antigen is often difficult. Primary amino-acid sequences reveal little information on how best to express a given antigen. What has been needed is a way to a...
Significant changes are sweeping the vaccine manufacturing industry. Demand for human vaccines is predicted to grow significantly — in part driven by needs in emerging countries, where only small fractions of their large and growing populations has access to vaccines. Sustained growth is expected to yield a vaccine market of US$25 billion by the year 2015 (
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Relatively low immunization rates in the Asia–Pacific regions represent significant untapped potential for vaccine manufacturers. Growing populations, increased government funding, and increasing personal wealth leads to more money being spent on improving personal health overall. Estimates of vaccine growth range as high as 65% in the Asia–Pacific. Significant vaccine-related investments are flowing into the region as many industry leaders establish research and development centers and expand their Asia–Pacific manufacturing capacity. China’s National Development and Reform commission is partially sponsoring investments and notes that development...
+2A novel influenza A (H1N1) virus was discovered in Mexico in early 2009 (
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). Infections from this strain led to declaration of a pandemic midyear, with about 61 million patients and 13,000 deaths reported by the US Centers for Disease Control (
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). Although the pandemic officially ended in August 2010 (
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), vaccines are still in demand to protect people against the H1N1 strain that is now expected to circulate seasonally for years to come. To best respond to pandemic outbreaks and annual composition changes, the vaccine industry must be able to produce large quantities of product in a short amount of time (
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). New methods for culturing, clone screening, scale-up, and production require analytical methods that can rapidly quantify virus to ensure enhanced productivity. Ideal new virus quantification methods would be fast, precise, robust relative to a wide range of viruses, and would correlate well with established methods (
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Established methods for influenza virus quantification include viral pl...
+3 On 28 June 2011, the Food and Agriculture Organization of the United Nations declared the Rinderpest cattle plague virus to be the second troublesome virus (after smallpox) that humans have eradicated from the Earth (
1
). Such achievements herald exciting times both for classical vaccinology and for many new and developing technologies. Here we consider scaling up of vaccines and related hybrid, targeted, and conjugated viral therapeutics that are made through animal cell culture. The vaccine industry is now moving from production in platforms based on whole animals and primary tissues (e.g., embryonated chicken eggs) to cultured-cell–based production (
2
). This transition began over 50 years ago with polio vaccine development. It is still in progress today, as evidenced by Baxter International’s recent European introduction of influenza vaccine produced by Vero cell culture. And the soon-to-open Novartis plant in Holly Springs, NC, one of the first producing flu vaccine by cell culture in the United St...
Seasonal influenza affects millions of people around the world, with as many as 500,000 deaths annually resulting from influenza-related illnesses. The flu virus undergoes frequent and unpredictable mutations (antigenic drift and shift) that limit the ability of available strain-specific vaccines to protect the population against strains other than those specifically included in a particular season’s flue vaccine. Annual reformulation of the vaccines is needed for annual immunizations.
BiondVax Pharmaceuticals Ltd., an Israeli biotechnology company, is developing a universal influenza vaccine (Multimeric-001, currently in phase 2 clinical testing) designed to be effective against all strains of influenza and eliminate the need for repeated annual immunizations. A phase 2 trial and two phase 1–2 clinical trials have been completed. In all three trials, the vaccine was shown to be safe and immunogenic, successfully stimulating both humoral and cellular immune responses.
Multiepitope Approach
Multimeric-001 ...
Picture rows and rows of chicken eggs incubating not to hatch chickens, but to produce vaccines. With the exception of a few products on the market now, most vaccines are still made using this 50-year-old technology. Using chicken eggs to produce vaccines takes about half a year to complete and requires on average one to two eggs to make a single vaccine dose. It is inefficient, labor intensive, time consuming, and subject to contamination. The latter may be the most important problem. In addition to the vaccine you want, contaminants (including other viruses) can get into the product stream.
But there may be a way to modernize our vaccine technology. Rather than producing a virus or a protein to inject into an organism, we can produce a sequence of DNA that has been genetically engineered to express proteins from a specific pathogen when introduced into an organism. The idea is that once the organism’s cells have made the proteins from that DNA sequence, the immune system will recognize them as foreign a...
Vaccines represent one of the most important medical developments in human history. As recently as a century ago, infectious diseases were the main cause of death worldwide, even in the most developed countries. For instance, the Spanish flu pandemic of 1918 killed more people than all the bullets and bombs did during World War I (
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Today, a vast range of vaccines are available to protect against more than two dozen infectious diseases, especially in pediatrics. Our society has found that the only way to control or even eliminate certain diseases is consistent, widespread use of vaccines.
Conventional vaccines are generally, excellent generators of antibody responses. Vaccine-generated antibodies can bind to various outer parts of viruses, bacteria, or toxins circulating in the bloodstream and as such, prevent the pathogen from establishing an infection. However, this mode of action limits conventional vaccines to preventing infection only if an individual is immunized before initial exposure to a giv...
Conference themes and approaches can be looked at as sort of a crazy quilt representing the state of the industry: with pieces of all different shapes and colors that come together to form a cohesive whole. They fit together in many ways, depending on the organizers (quilters?); many pieces are omitted and saved for the next quilt. But how to find the most successful combinations requires technique as well as imagination.
Here are some topics I’ve been enjoying this year so far. The annual WCBP conference and related CMC Strategy Forum early in the year are always good venues. We publish the forum’s resulting consensus papers, as you know. The particulates discussion this year was especially timely in light of new analytical techniques — and we’ll publish that paper this fall.
I returned to DC for the Phacilitate Cell and Gene Therapy conference, during which my publisher and I worked to finalize our cell therapies supplement (May). Becoming more conversant with the vocabulary and science of regenerative ...
In the early spring of 2009, a new strain of H1N1 influenza emerged and swept across the globe more rapidly than vaccine producers could keep pace. By the time the pandemic abated in February 2010, the US Centers for Disease Control (CDC) estimated that between 8,500 and 17,600 Americans had died from H1N1 infection, with a disproportionate number of deaths occurring among healthy children and young adults. An estimated 15–25% of the nation’s population was exposed to the virus.
However, production of vaccine against this aggressive new influenza strain was agonizingly slow. A total of 18 weeks passed between identification of the new virus and the start of the pandemic’s “second wave” — 26 weeks to the peak of that second wave. But the first doses of vaccine did not become available until 26 weeks after strain identification, when spread of the virus was already at its zenith. Vaccine doses sufficient to protect 50% of the US population became available at 38 weeks, and doses to protect 100% of the popul...
