Vaccine against dental caries--a personal view.

Abstract

S everal decades have elapsed since the concept of a vaccine based on antigens derived from Streptococcus mutans began to be explored. As the literature on this topic has accumulated, the origins of this concept and its development have become clouded in the mists of time. In addition, there are clear differences of opinion as to the most appropriate immunogen and, furthermore, whether the protective antibody must be in sIgA or IgG. As our understanding of the etiology and pathogenesis of dental caries is enhanced, it becomes increasingly clear that the development of an effective, safe caries vaccine may not be as readily achieved as originally conceived. The purpose of this paper is to explore, from strictly a personal perspective, the evolution of the concept and to assess what the future may hold. In 1959 when I completed my training at the Eastman Dental Center and the University of Rochester, I applied for a research fellowship in the newly formed Department of Dental Research in the Royal College of Surgeons, London, England. There I met Sir Wilfred Fish and Bertram Cohen. Fish was one of the most dynamic, enthusiastic, helpful persons one could wish to meet. Every area of dental research he investigated-from prosthetics and periodontal disease to dental caries-was enhanced by his contributions. He had the uncanny knack of reducing apparently complex subjects to their simplest terms. In the course of his career, Wilfred Fish held many influential positions, including oral surgeon in St. Mary's Hospital, Paddington, London. It was there he met Almoth Wright, Alexander Fleming (Flem, as Fish referred to him), and Killian Clarke. Fish, because of his association with Clarke, had no doubt that Streptococcus mutans was the main microbial culprit in dental caries. So, from the earliest part of my career, I was exposed to the importance of S. mutans, so elegantly described by Clarke in 1924. Until I met Fish in 1959, like many researchers in the USA and Britain at that time, I considered lactobacilli to be the primary microbiological culprit in the etiology of dental caries. When Clarke published his work, a controversy erupted, led by the lactobacillus camp of McIntosh, James, and Lazarus-Barlow (1922). I was told by Fish that the debates were frequently vitriolic and highly personal. I had the pleasure of meeting James when he was in his 80s, by which time he had mellowed just a little. A brief perusal of the microbiological literature in the late 1930s through almost 1960 reveals the virtual disappearance of S. mutans from the scientific literature. Unfortunately, Clarke did not place any of his isolates in a type culture collection, in contrast to McIntosh and colleagues, who deposited what they termed acidophilus types I and II in the British Type Culture Collection. When examined some years later, these were found to be Lactobacillus plantarum. There is little doubt that the forceful personalities of the lactobacillus proponents contributed to the virtual disappearance of S. mutans from the literature. An additional reason may be found in the absence of an appropriate animal model to support the importance of S. mutans in the etiology and pathogenesis of dental caries. Although McCollum et al. had described caries induction in rats in 1922, and Wallace had successfully produced caries in a primate in 1901, both studies focused on the dietary aspects of caries to the virtual exclusion of the importance of micro-organisms. It is perhaps somewhat ironic that, even today, despite all the major advances, there are many who fail to comprehend the uniqueness of dental that it is a dieto-bacterial disease. One suspects that Clarke would have made rapid advances in elaborating the role of S. mutans in the etiology of caries if an animal model had been readily available to him. Maclean (1927) and later Fish and Maclean (1934) grasped the potential importance of an appropriate animal model, and the significance of identifying a single microbial culprit. This was demonstrated in their paper, Immunity to the organisms of dental caries, where they described some experiments they performed using monkeys. Little attention was given to the concept of vaccination or immunity to dental caries for almost a decade when Canby and Bernier (1942) published their paper followed by two papers by Williams (1944a,b) describing vaccination of humans against dental caries using lactobacilli. How attitudes toward human experimentation have changed over the decades! It is difficult to assess the outcome of Williams' experiments. Even though he did report a reduction in the population of lactobacilli, caries was not assessed. Interest in vaccination against caries languished for many years until the importance of S. mutans in caries etiology was rediscovered primarily by Zinner et al. (1964) who were collaborating with Fitzgerald, although Sims (1970) had already placed an isolate of S. mutans in the British Type Culture Collection, which many believed, erroneously, was Clarke's original S. mutans. Zinner's work