The Changing Landscape of Global Vaccine Development and Market Potential - - BioPharm International


The Changing Landscape of Global Vaccine Development and Market Potential

BioPharm International
Volume 20, Issue 10

A universal influenza vaccine(with cross-protective antigens), targeting all "A" strains of the virus, is in Phase 1 clinical development in the US. "A" strains historically have been responsible for influenza pandemics. This vaccine targets both seasonal and pandemic influenza strains, and eliminates the annual rush to re-engineer and manufacture sufficient vaccine supplies. The vaccine focuses on the M2 protein of the influenza A virus, the extracellular part (M2e) of which is highly conserved in all A strains. The conserved M2e domain is genetically fused to a hepatitis B virus core protein (HBc) and expressed in E. coli.

The FDA approved the first US vaccine for humans against the highly pathogenic avian influenza H5N1 virus in April 2007. Other avian influenza viruses, like H7N7 and H9N2, are being evaluated as vaccine targets for a possible pandemic avian flu outbreak.

HIV Vaccines

Despite 25 years of extensive efforts in developing HIV vaccines, no licensed vaccine is available today. The difficulties include high genetic variability of the virus, lack of knowledge of immune correlates of protection, inability to generate broadly neutralizing antibodies, absence of relevant and predictive animal models, and the complexities related to the preparation and conduct of multiple, large-scale clinical trials.11–12

Early investigations were mostly focused on inactivated virus, live-attenuated virus, and recombinant proteins. Although these candidates showed immunogenicity and protection in animal models, clinical studies have not demonstrated protection against the disease in humans. Recent clinical trials are more focused on plasmid DNA and recombinant live vectors, and have used either simple or multiple antigens from both structural and nonstructural HIV proteins to invoke a T-cell response.11 A DNA vaccine using a codon-optimized gp140 from a primary (non-recombinant) HIV-1 subtype C isolate was shown to induce both humoral and cell-mediated responses13 although constructs containing Gag-protease, Tat-Rev-Nef, Tat, and Gag were all shown to induce cell-mediated response.14–17 A canarypox virus vector (ALVAC) has been developed by Sanofi-Pasteur and evaluated in multiple clinical studies.18 Recent clinical studies used a propagation-defective alphavirus replicon derived from an attenuated strain of Venezuelan equine encephalitis (VEE) virus and expressed the Gag gene from a South African HIV-1C isolate.19

Therapeutic vaccination for HIV is also an active area of research and development.20–21 It is hoped that the HIV patients' own anti-HIV immune responses can be strengthened by these vaccines so that the patients will not have to rely exclusively on antiretroviral drugs.22 Several recent reports showed preliminary positive results using a recombinant canarypox vaccine and dendritic cells loaded with heat-inactivated autologous HIV-1.21,23 Other studies used plasmid DNA with various adjuvants and delivery systems.

Cancer Vaccines

The concept of therapeutic vaccines against cancers has been around for many decades, starting with the nonspecific immunostimulatory approaches first used by William Coley24 and progressing to more tumor-specific approaches such as autologous and allogenic tumor cell vaccines, and heat-shocked proteins.25 Considerable advances have been made over the past few years in developing cancer vaccines using whole-cells, proteins or peptides, plasmid DNA, and viral vectors with new adjuvants.26

Natural or synthetic peptides and recombinant proteins as vaccines targeting tumor-associated antigens, have shown promising results in humans. A peptide vaccine targeting melanoma melanocyte differentiation antigens (MART-1, gp100, and tyrosinase), was shown to elicit immune responses and prolong relapse-free survival.27

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