Antibodies, vaccines and adjuvants - Pharmaceutical Biotechnology: Concepts and Aapplications - page 412

Table 13.12 Some putative HIV vaccines which have made it to clinical trials

Vaccine preparation Developing company

Inactivated viral particles Immune Response

rgp 120 subunit vaccines Genentech/Vaxgen, Biocine, Chiron/Ciba Geigy

rgp 160 subunit vaccines MicroGenes Sys. Inc., Immuno-Ag.

rp 24 subunit vaccines MicroGenes Sys. Inc.

Live vaccines based on viral vectors Biocine, Merck, Sanofi Pasteur, Targeted Genetics

Octameric V3 peptide UBI

response, in particular a cytotoxic T-cell response (now seen as critical to mounting an effective
immune response), explains at least in part why subunit vaccines were a clinical disappointment.
Several HIV vaccine systems based upon live vectors have also been developed in an attempt
to stimulate a signifi cant T-cell, as well as B-cell, immune response. Both envelope and core
antigens have been expressed in a number of recombinant viral systems. The clinical effi cacy of
these remains to be established. Expression in engineered vaccinia has been undertaken, but its
use as an HIV vaccine is likely precluded by the fact that the virus can apparently disseminate and
cause fatal encephalitis in immunosuppressed infected individuals. Modifi ed vaccinia Ankara,
canarypox and fowlpox viruses have come to the fore as vectors. These likely can produce suf-
fi cient protein to initiate both a humoral and cellular immune response during an abortive replica-
tion cycle in humans. A vaccination schedule variation of potential interest entails the use of a
vector-based primary dose (to induce a cellular response in particular) followed by a subunit-based
booster (to induce mainly a humoral response). Whatever the schedule however, the induction of
effective (i.e. broadly neutralizing) antibodies remains a challenge, as the regions of HIV envelope
proteins that are most highly conserved seem to be shielded from antibody access by loop struc-
tures and sugar side-chains on these surface proteins.
Large-scale clinical trials are likely to be the only way by which any HIV vaccine may be prop-
erly assessed. In addition, a greater understanding of the molecular interplay between the virus
and immune system may provide clues as to the development of novel vaccine and/or therapeutic
products. For example, a small proportion of infected individuals remain clinically asymptomatic
for periods considerably greater than the average 10-15 years. An understanding of the immuno-
logical or other factors that delay onset of ARC/full-blown AIDS in these individuals may aid in
the design of more effective vaccines.

13.4.8 Cancer vaccines

The identifi cation of tumour-associated antigens could pave the way for the development of a
range of cancer vaccines. A number of tumour-associated antigens have already been character-
ized, as described previously. Theoretically, administration of tumour-associated antigens may
effectively immunize an individual against any cancer type characterized by expression of the
tumour-associated antigen in question. Co-administration of a strong adjuvant (see Section 13.5)
would be advantageous, as it would stimulate an enhanced immune response. This is important,
as many tumour-associated antigens appear to be weak immunogens. Administration of subunit-
based tumour-associated antigen vaccines would primarily stimulate a humoral immune response.