Introduction: Emerging vaccine strategiesBrian Barber

TWO HUNDRED YEARS ago Jenner launched the era ofvaccination with the demonstration that disease couldbe prevented by deliberate inoculation. By the end ofthe 19th century, the work of Pasteur and hiscontemporaries had placed the development of newvaccines on a firm experimental foundation, andprovided further examples of disease preventionthrough immunization. The past 100 years have seena consolidation and extension of these earlier vaccineinitiatives, contributing collectively to a profoundbenefit in human health. The astounding eradicationof smallpox, and the great strides which have beenmade in moving viruses such as polio and measlestowards the same fate, are among the proud accom-plishments of vaccinology over the last 50 years.

Nevertheless, much more remains to be achievedthan has yet been accomplished in the area of vaccinedevelopment and application. The latter part of the20th century has seen the emergence of new infec-tious agents, such as the human immunodeficiencyvirus, which went from first sighting to an uncheckedglobal pandemic in less than a decade. There-emergence and continuing spread of old enemies,like tuberculosis and malaria, further highlight theneed to press for the development of new vaccinestrategies.

In this regard, it is interesting to note that the vastmajority of the currently licensed set of humanvaccine agents (approximately 25 in total) weredeveloped before immunologists could distinguish Bcells from T cells. Advances in our understanding ofthe immune system over the past 30 years could onlybe described as spectacular. Combined with paralleland equally impressive developments in molecularbiology, we are now in possession of the knowledgeand technologies which should permit the introduc-tion of a new generation of vaccine agents. However,the problems are difficult and the regulatory barriersappropriately high. Thus we find ourselves still in themidst of this great potential, continuing to explore

new strategies and opportunities for the prevention ofdisease by manipulation of the immune response.

The purpose of this volume is to review some of thealternatives presently being explored as new vaccinedesign options. Of necessity, the selection is limitedrather than comprehensive, but hopefully this set ofreviews will provide a perspective on current develop-ments in the field of vaccine design.

The first of these offerings is by Robinson andTorres in the area of DNA vaccines. The use ofbacterial expression plasmids as a means of inducingprotective immunity burst onto the scene about 5years ago. Recent developments in this area of intenseresearch interest indicate that this strategy has thepotential to completely revolutionize the way in whichvaccines are designed and delivered.

A further improvement in our understanding of theimmune system has been an increased appreciation ofthe way in which cytokines regulate inter-cellularcommunication. The recognition that specific cyto-kines promote certain types of immunity has revealednew possibilities for directing responses into thosepathways most appropriate for particular pathogens.Scott and Trinchieri review the use of IL-12, aparticularly potent cytokine, with respect to its abilityto usefully augment cell-mediated immunity againstdefined antigens.

One of the long-standing quests in vaccine develop-ment has been the search for safe and effective meansto augment immune responses to defined non-selfantigens. Collectively these immunostimulatory sub-stances are known as adjuvants, and the very limitedset of these formulations which are currently licensedfor use in humans represents a major constraint onthe introduction of new subunit vaccines. Barber hasreviewed an adjuvant-independent immunizationstrategy known as immunotargeting, which promotesantibody responses to defined epitopes delivered toantigen presenting cells in vivo by targeting mono-clonal antibodies.

The review by Rosenthal and Gallichan explorestwo important issues in modern vaccine research; theuse of recombinant viral vectors as a means ofinducing immunity to a heterologous infectiousagent, and strategies for promoting mucosal immune

From the Department of Immunology, Faculty of Medicine,Medical Sciences Building, University of Toronto, 1 King’s CollegeCircle, Toronto, Ontario M5S 1A8, Canada

seminars in IMMUNOLOGY, Vol 9, 1997: pp 269–270

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responses at epithelial cell surfaces. More specifically,they have examined the use of adenovirus vectors asinducers of both B- and T-cell immune responses toherpes virus antigens in the female genital tract.Effective means of invoking strong mucosal immunitywill be important for vaccines designed to block bothenvironmental and sexually transmitted infectiousagents.

Although the term ‘vaccine’ has traditionally beenapplied to an immunogen designed to prevent diseasecaused by an infectious agent, over the past decadethis definition has been increasingly extended toinclude immunization for therapeutic purposes aswell. In this context, there has been a recent surge ofinterest in the development of immunogens designedfor the treatment of cancer and autoimmune disease.Li has reviewed one of the more provocative develop-ments in the area of cancer vaccines; the use oftumour-derived heat shock proteins as anti-cancerimmunogens. The exciting possibility of developingan individual, tumour-specific immunization strategybased on the heat shock proteins ensures that thispotential will be intensively investigated over the nextfew years.

One of the principal reasons for the renewedinterest in the possibility of inducing anti-cancerimmunity is the recent identification of defined,tumour-specific T-cell epitopes. Coupled with a grow-ing appreciation of how these epitopes can be madeinto potent T-cell immunogens, the potential todevelop effective anti-tumour vaccines based on thisknowledge moves closer to practical application. Inthe final review in this volume, Toes and colleaguesexplore the promise and the problems associated withbringing these approaches to fruition.

As we approach the end of the 20th century, it isclear that both the potential and the need to expandour ability to prevent and treat disease throughimmunization has never been greater. At the sametime, it is equally clear that a concerted effort acrossthe full spectrum of basic and applied immunologywill be required to translate this potential into thereality of new vaccines and improved human health.Hopefully achieving these goals will be among theearly accomplishments of the next century.

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