Elsevier

Vaccine

Volume 27, Supplement 4, 5 November 2009, Pages D8-D15
Vaccine

Technical transformation of biodefense vaccines

https://doi.org/10.1016/j.vaccine.2009.08.055Get rights and content

Abstract

Biodefense vaccines are developed against a diverse group of pathogens. Vaccines were developed for some of these pathogens a long time ago but they are facing new challenges to move beyond the old manufacturing technologies. New vaccines to be developed against other pathogens have to determine whether to follow traditional vaccination strategies or to seek new approaches. Advances in basic immunology and recombinant DNA technology have fundamentally transformed the process of formulating a vaccine concept, optimizing protective antigens, and selecting the most effective vaccine delivery approach for candidate biodefense vaccines.

Section snippets

Changes in manufacturing processes

Anthrax bioterrorism attack that ensued in the U.S. shortly after September 11, 2001 was the key turning point in the history of biodefense vaccine development. Suddenly, the need for biodefense vaccines became eminent and moved from the traditional military market (i.e., protecting soldiers from biological weapons) to one incorporating both military and public use. However, many problems associated with the production of early generations of biodefense vaccines were also exposed. Vaccines for

Correlates of immune protection

Traditionally, it has been postulated that vaccines are effective through the induction of protective antibodies in the host. In recent years, with the availability of more sophisticated biomarker assays that were initially developed for routine human vaccines, the roles of T cell immune responses have been better recognized in biodefense vaccine studies.

One surprising finding came from plague vaccine studies. Smiley and colleagues showed that B cell-deficient mice vaccinated with live

Subunit protein or gene-based vaccination approaches

Traditional biodefense vaccines were designed by using either live attenuated or inactivated vaccine approaches. As discussed in the above sections, live attenuated vaccines have the benefit of normally inducing stronger protective immunity than inactivated vaccines but are not ideal candidates when facing the challenges related to manufacturing processes or more critically, to improve the overall safety profile of biodefense vaccines. Furthermore, regulatory authorities expect to see the

Future outlook

Since 2001, biodefense vaccine development has experienced significant progress in the areas of manufacturing, immunological mechanisms and novel vaccination approaches. There are other unique issues not covered in this technology review but they are equally important for biodefense vaccine development. These include 1) “animal rule” which applies to vaccines unable to conduct a late phase large scale efficacy trial in humans due to the rare natural occurrence of such infections; 2)

Acknowledgement

Authors are supported in part by NIH NIAID grant U01AI078073.

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