Building New Vaccines

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Cold Spring Harbor meeting HBsAg2. This cyclic form of the peptide gave a much better antibody response than the linear form. Building new vaccines A quite novel way of overcoming the need for carrier proteins and adjuvants from Nigel Williams may be the use of recombinant vaccinia virus as a live vector to present heter HEPATITIS B virus may be one of the first recombinant HBsAg DNA in cell vectors. ologous virus subunits. M. Mackett (NIH) viruses to come under large-scale attack Valenzuela et 01.1 and subsequently described the production of vaccinia from a synthetic subunit vaccine and, if an others identified the part of the hepatitis B recombinants expressing HBsAg4. acceptable way of boosting the immune genome encoding the 226 amino acids of Vaccination of three chimpanzees with response can be found, many more viruses the HBsAg by cloning viral DNA in these recombinants provided total pro face a similar challenge. One unorthodox Escherichia coli. The use of E. coli for vided total protection when the animals way of tackling this problem may be to use expression however, has been difficult; but were subsequently challenged with HBV recombinant vaccinia virus, a descendant using yeast cells as vectors, W.N. Burnette (G.L. Smith, NIH). E. Paoletti (New York of Jenner's original protocol against (Amgen) and D.E. Wampler (Merck, State Department of Health) reported on smallpox, as a vector. With the focus on Sharp and Dohme) were among those other vaccinia recombinants expressing the viruses, these were some of the points reporting successful expression. The coat glycoprotein (gO) of herpes simplex arising from the first of what promises to be molecule is not glycosylated or secreted but virus, that were able to protect mice from an annual series of meetings to consider the forms aggregated particles in yeast cells subsequent, normally lethal, challenge modern approach of vaccines. • which appear similar to those recovered with live virus. The modern approach is dominated by from serum. The yeast derived particles These are impressive results but the use efforts to produce synthetic subunit seem as potent as the plasma derived of a live recombinant vector for subunit vaccines which, in the long term, may be particles in stimulating antibodies; indeed, vaccination in man is clearly controversial. able to overcome problems of con Wampler reported that the Merck, Sharp Among the many potential problems are tamination and storage often found with and Dohme product, purified by immune the possibly different and more dangerous conventional vaccines. Also, viruses for affinity, is about to undergo clinical trials. tropisms of recombinant viruses and which there are no conventional vaccines Since publication of the first nucleotide reversion of recombinants to a more can be tackled. Because it appears that only sequence of HBsAg, several groups have virulent form. However, the enormous a restricted number of sites on the viral also produced synthetic peptides corres worldwide experience (and undoubted surface are important targets for ponding to specific regions of the success) in using vaccinia virus for small neutralizing antibodies, the aim is to molecule. So far the ability of such pep tides pox vaccination and the impressive produce synthetic analogues of these to induce antibodies that cross-react with immunogenicity of the recombinants regions by expression of viral proteins in native HBsAg has been surprisingly good suggest that it is well worth tackling these recombinant heterologous cells or by but the strength of the response has been potential problems. chemical synthesis of short peptides. If variable and difficult to predict. However Although the problem of boosting the such subunits retain the configuration R.A. Lerner (Scripps Clinic) has response to subunits may be overcome, the found normally on the viral surface and encouraging results with a peptide of 38 problem of antigenic lability of certain can induce a specific immune response, the amino acids in length spanning a relatively viruses remains. Foot and mouth disease hope is that they can form the basis of safe hydrophilic region of HBsAg. In a trial on virus (FMDV) appears to have a dominant and effective vaccines. three chimpanzees one was protected, one neutralizing site on the capsid protein, The appeal of this approach was developed infection without disease and VPl. Synthetic peptides spanning the reflected by the number of groups one developed acute infection when subse region have been produced and are able to reporting work on a wide range of animal quently challenged with HBsAg. But a induce protective antibody in rabbits and human viruses. While many have problem with this and many other pep tides against the corresponding FMDV strains. obtained antibodies to synthetic products is that a carrier protein and adjuvant are But FMDV is extremely labile and exists in that cross-react with the intact virus, this is needed to boost the immune response; the many variant forms. D.J. Rowlands only the first step - a potential vaccine majority of these agents are unacceptable (Animal Virus Research Institute, must stimulate an antibody response for use in man. Pirbright) described three antigenic strong enough to protect the animal from Encouraging for a different reason is the variants within a single isolate which differ subsequent infection. It is clear that this is a production (E. Wimmer, SUNY Stony at only two amino acids within the major challenge. Brook) of several peptides representing immunogenic site. Pep tides representing Hepatitis B virus is of particular interest regions of the poliovirus (type 1) capsid the immunogenic site of the different because no conventional mass vaccine protein, VPP. Although only one peptide variants induce good neutralizing antibody exists against this virus - the cause of was able to induce neutralizing antibodies only against the corresponding variant. widespread and serious human disease - in rabbits, when attached to a carrier The antigenic lability of FMDV suggests but a natural, highly immunogenic protein and injected with adjuvant, all the that a synthetic vaccine may have to 'subunit' can be found in the serum of peptides were able to prime the immune comprise several different peptides tailored chronically infected individuals. This response so that the animals responded each time to cope with local FMDV consists of particles containing aggregated vigorously to a subsequent challenge with variants. viral surface antigen (HBsAg) molecules in whole virus vaccine. It may be that priming The power of the subunit approach both glycosylated and non-glycosylated an immune response is sufficient to protect which allows the viral surface to be forms. Purification of these particles from an individual against viruses with a long explored and the nature of specific serum has formed the basis of a small-scale incubation time but again, the carrier antibody-antigen interactions examined, but successful vaccine by Merck, Sharp ladjuvant system used puts human use justifies the optimism and the growing and Dohme. It is the proven potency of some way off. interest in these techniques. 0 these particles (and their very limited G.R. Dreesman (Baylor College, supply and high cost) that has been the Houston) described one way that may Nigel Williams is assistant editor of Nature. impetus for obtaining expression of overcome the need for a carrier protein; he J. Valenzuela. p, et 01. Nature 280, 815 (J979). has introduced a cross-linking disulphide 2. Dreesman. G.R. el 01. Nalure 295,158 (1982). ·Modern Approaches to Vaccines: A meeting held at the Cold bond into a peptide, 16 amino acids in 3. Emini, E.A . el 01. Narure 304, 669 (1983). Spring Harbor Laboratory. New York. 31 AUiust-4 September 4. Smith. G.L. el 01. Nalure 302. 490 (1983) 1983. length, corresponding to a region of 5. Bitte. J.L. el 01. Nalure 298. 30 (1982).