Applications and challenges of multivalent recombinant vaccines

Figures & data

Table 1. Vaccine Designs and strategies in light of their use against HIV

Vaccine Design	How Does this Vaccine Work?	Critical issues
Viral Proteins or Viral Peptides ^7	Chemically synthesized or produced by mammalian cell lines or Bacteria. These pieces of HIV peptides or proteins that elicit strong T and B cell responses are formulated with lipids and adjuvant in order to induce significant immune responses.	Peptide-based preparations require the addition of an adjuvant to enhance immunogenicity. At present, alum is the only adjuvant authorized by FDA for general medical use, however many alternative products are being tested likely in clinical trials.
DNA ^9	Target genes are inserted into a specific site in the backbone of DNA (known as plasmid), under the control of certain promoter to efficiently express the gene. The DNA (vaccine) is injected into muscle of the recipient where the target genes are expressed into proteins. These proteins are then degraded into small peptide fragments, which are presented by MHC I and II molecules on the cell surface to activate humoral and/or cellular responses.	Clinical trials did not show conclusive efficacy yet. Except for clinical trials, DNA vaccines have not yet been licensed for use in humans by the FDA.
Viral (Live or replication deficient) or bacterial vectors^13^-^17	The HIV or SIV genes are inserted into the genomes of live, infectious, but non-disease-causing forms of viruses (e.g., adenovirus, poxvirus, measles virus) or bacteria (e.g., Bacille Calmette-Guerin (BCG). These vectors shuttle “foreign” genes along with their own into cells. HIV proteins generated from these recombinant genes inside the cell are either secreted or displayed on the cell surface and presented to the immune system.	The development of viral vectors has been robust, with a few entering Phase III trials. Only a few bacterial vectors are under development in small and large animal models, and some Phase I trials. The complex nature of bacteria hampers the development of bacterial vector systems.
Virus-like Particles (VLPs) ^23	Empty, non-infectious shells of the HIV envelope protein; they mimic the outer coat of the virus but lack a genome inside and cannot reproduce. Because VLPs resemble the virus, they can induce high titers of neutralizing antibodies to protect against viral challenge.	VLPs represent an exciting new strategy for HIV vaccines but it has been difficult to make them reproducibly.

Figure 1. Comparison of the cloned MV vaccine with various commercially available MV vaccine strains and a “lab-strain.” (A) Transgenic mice expressing human CD46 were immunized i.m. with 1 × 10⁴ pfu of an authentic cloned vaccine (rMVb), a Moraten vaccine (MVbv), Edmonston Zagreb vaccine (MVEZII) and a “lab strain” MVtag. Measles end point titers are shown on a logarithmic scale. (B) Growth kinetic analyses. Comparison of the propagation kinetics of the standard MVbv, cloned MVb and the MVEZII compared to the “lab strain” MVtag. Sub-confluent Cells were infected with the designated viruses and incubated at 31°C, media were collected every day up to 6 days. The shed viruses were titrated by plaque assays.

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