Study supports Prima vaccine effectiveness

By Graeme O'Neill
Tuesday, 15 November, 2005

A research report in the international journal Vaccine this month has confirmed the immunity-boosting potency of Prima Biomed's (ASX:PRR) novel DCtag adjuvant technology for veterinary vaccines.

The Vaccine article reported that sheep injected with polystyrene nanobeads carrying the chicken-egg protein ovalbumin exhibited strong antibody and T-cell responses to the model antigen.

DCtag technology is based on the discovery by Assoc Prof Magda Plebanski, of the Austin Research Institute, that antigens presented on virus-sized particles (~50 nanometres) elicit strong humoral (antibody-mediated) and cellular (helper-inducer and cytotoxic T-cell) immunity.

DCtag is a technology for 'priming' dendritic cells (DCs), specialised sentry cells that detect and dissect infectious microbes and viruses. DCs display the resulting antigens to the immune system, which responds by producing antibodies and T-cells to the quell the infection.

Most conventional vaccines elicit only humoral immunity; their failure to produce a strong cytotoxic response has confounded immunologists for decades. A cytotoxic response is essential for eliminating cells harbouring replicating viruses, bacteria or parasites, which are beyond reach to antibodies.

Poor T-cell responses have also impeded the development of anti-cancer vaccines. T-cells play a critical role in immunosurveillance -- they work together to destroy pre-cancerous cells displaying mutant proteins that have been 'labelled' for destruction by antibodies.

Plebanski is chief scientific officer with Prima subsidiary PanVax, Last year her research team showed that a DCtag 'nano-vaccine' inhibits the growth of tumours in mice, and produced strong immunity to mutant proteins on the surface of cancerous cells.

In their latest experiments, the ARI researchers, working with Dr Jean-Pierre Scheerlinck's team at the Centre for Animal Biotechnology at the University of Melbourne, compared the efficacy of a DCtag-boosted ovalbumin nano-vaccine against that of a conventional vaccine that used alum (aluminium hydroxide).

The sheep tolerated the DCtag vaccine well, whether it was delivered by the intradermal subcutaneous, or intramuscular route. In each case, it produced strong humoral and T-cell immunity, where the alum-boosted vaccine produced only humoral immunity.

Alum is the only adjuvant approved for use in human vaccines. It is far from ideal -- it elicits strong humoral immunity, but not T-cell immunity. It also causes inflammation at the site of injection.

Prima said that while other adjuvants are approved for veterinary vaccines, DCtag could meet the need for a more effective adjuvant technology for both human and veterinary vaccines.

The ARI researchers have been experimenting with polystyrene, silica, gold and iron nanobeads, and other biocompatible materials -- the size of the particles, rather than their composition, appears to be critical to generating a two-armed immune response.

Plebanski said the finding that DCtag was effective and well-tolerated by sheep was an important step in the progression towards clinical studies of the technology in humans. "We believe that the technology wil be applicable to the prevention of human and animal diseases caused by viral and parasitic pathogens,' she said.

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