The
VesiVax® system is a liposome-based antigen delivery platform
technology that is designed to deliver both target antigens and IAMs together
in well-defined ratios. Through years of research and development, we
engineered the VesiVax® system to consist of a novel formulation of
lipids that has been optimized for immunogenicity and shelf stability. One of
the features of the VesiVax® system is that antigens can be
engineered to be compatible with the liposomes via a flexible and easily modified plasmid vector that can produce
antigen-hydrophobic domain (HD) fusion proteins. Recently, the technology was further expanded
to allow for direct conjugation of antigens to the liposomes (Figure 1).
With the aid of multiple collaborators, we have demonstrated the ability of the
VesiVax® system to stimulate protective immune responses in a
variety of animal models (i.e., mice, rats, guinea pigs, chickens, pigs,
rabbits, ferrets, and non-human primates) with a range of antigens (i.e.,
small molecules (~300 Da), peptides, large protein complexes (>100kDa) and
virus-like particles (VLPs)). Collectively, our studies have shown that the
VesiVax® system elicits a stronger immune response to the antigen of
interest than 
conventional carriers (e.g.,
bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH)) and adjuvants (e.g.,
alum and squalene oil-in-water based carriers).
Many innovative features have been engineered
into the VesiVax® vaccine and adjuvant system. 1)
Ease of use – the conjugation reactions with antigens/peptides
containing sulfhydryl groups have been optimized and well characterized. The
conjugation procedure is straightforward; antigens can be easily conjugated and
are ready for immunization in 1-2 h. In addition, we have developed VesiVax®
conjugation strategies that can target a spectrum of antigens which may contain
carboxyl, amine, or hydroxyl groups. 2)
Flexibility – the VesiVax® system has been designed such that
it can incorporate different and/or multiple IAMs (e.g., TLR ligands)
together with one or more antigens. The dosages of the adjuvant(s) and
antigen(s) can be easily manipulated such that the maximum immune response can
be achieved. 3) Immunogenicity 
– the basic VesiVax® formulation was determined by critical
evaluation of the lipid compositions that effectively stimulate immune
responses. 4) Scalability – the
formulation process is easily translatable into large-scale, cGMP
manufacturing, to supply millions of doses of a cost-effective vaccine. 5) Stability – manufactured lots of
VesiVax® liposomes have been tested and shown to be stable for over
1.5 years. Taken together, the features of the VesiVax® platform
technology are anticipated to address the need for an easy-to-use, potent
adjuvant system that can be used to accelerate vaccine development efforts.
The recent development of VesiVax®
IAM formulations displaying conjugatable moieties from the surface of the
liposomes was aimed at accelerating the identification and development of new
vaccines. Several VesiVax®
conjugation chemistries have been developed (see Figure 1). The most commonly used conjugation molecule is a
proprietary cholesterol-maleimide (CMI) which has been extensively tested by Molecular
Express. In this system, VesiVax®
formulations containing CMI react with sulfhydryl-containing molecules (e.g., either the antigen or receptor
molecules on the surface of immune cells) to form stable thioether bonds. This
reaction happens readily at physiological conditions i.e., pH 6.5 – 7.5. The maleimide groups on the VesiVax® liposomes stay
stable and remain available for conjugation even after 83 weeks (>1.5 years)
of storage at 4ºC (Figure 2). The optimal concentration of maleimide groups displayed on the surface
of the VesiVax®
liposomes and the ideal conditions for shelf storage have been determined.
