Synthetic peptides: a next generation of vaccines?

Of the strategies being considered in the search for new kinds of vaccine, one of the most powerful is the use of synthetic peptides. Here, Michael Steward and Colin Howard discuss recent insights into the nature of antigenicity which influence the use of such peptides, and review the value of peptide immunogens in a variety of diseases.

HBsAg: anti-HBs immune complexes. A method for separating the constituent components and assessment of the affinity of the antibody.

A number of chemical disruption agents were assessed for their ability to dissociate HBsAg:anti-HBs immune complexes and to release both the antibody and antigen component in immunologically active forms. The most appropriate reagent was 0.1 M diethylamine which could elute up to 81% of anti-HBs antibody bound to solid-phase HBsAg and retained 93% of its antigen-combining activity.

Work and defensive processes in small groups: effects of leader gender and authority position.

The effects of leader gender and degree of authority on work activity and group-as-a-whole defensive processes were examined in two Tavistock-model group relations conferences. The small groups in each conference had two leaders with different degrees of explicit authority, a consultant and associate consultant. In one conference, males were designated as consultants and females as associate consultants.

A surrogate hepatitis B virus antigenic epitope represented by a synthetic peptide and an internal image antiidiotype antibody.

The use of molecules that represent single, defined epitopes able to substitute for antigen (i.e. surrogate antigens) offers considerable advantages over the use of native antigen for the precise manipulation of the immune response.

Antibody responses to recombinant and plasma derived hepatitis B vaccines.

The antibody response to hepatitis B surface antigen (anti-HBs) induced in 25 recipients of a recombinant hepatitis B vaccine derived from yeast was compared with that induced in 25 recipients of a vaccine prepared from hepatitis B surface antigen (HBsAg) derived from plasma. Anti-HBs affinity and specificity were compared using assays of antibody affinity with two different antigens, a complex of the major polypeptide of HBsAg (p25; molecular weight 25 000 daltons) covalently linked to its glycosylated form (gp30) prepared from native purified HBsAg, and a cyclical synthetic peptide representing amino acid residues 139-147 of the major polypeptide of HBsAg and known to represent a major part of an a determinant. There was no difference in anti-HBs affinity or molar antigen binding sites of the antibody measured with either antigen between the two groups.

Antibody affinity maturation in selectively bred high and low-affinity mice.

The affinity of serum antibodies produced by selectively bred lines of mice [high affinity, low affinity, low nonmaturing (N/M)] injected with T-dependent [human serum albumin (HSA), dinitrophenylated bovine gamma-globulin (DNP-BGG)] and T-independent (DNP-Ficoll) antigens in saline and adjuvant has been determined. The lines of mice differ significantly in the affinity of antibody produced to T-dependent antigens injected in saline but not to the T-independent antigen. Unlike mice of the high and low-affinity lines, low-affinity N/M mice failed to show affinity maturation to HSA and DNP-BGG injected in Freund's incomplete adjuvant.

Variations in host responses and the pathogenesis of human onchocerciasis.

Different immune responses to Onchocerca volvulus cause considerable variation in clinical manifestations of human onchocerciasis. Onchocercal lesions result from inflammatory reactions involving immunologic mechanisms; the role of the immune system in pathogenesis is emphasized by the phenomena accompanying accelerated worm destruction during microfilaricidal chemotherapy (e.g.

Prediction of response to treatment in chronic pain patients.

A seven-item rating scale reported by researchers from the Mayo Clinic to have high validity in identifying chronic pain patients who would benefit from inpatient treatment was administered to an outpatient sample. Initial results did not replicate the previous findings; inclusion of four additional variables (disruption of a close relationship, altered body image, history of childhood illness, and history of abuse in childhood) produced results comparable to the Mayo study. This expanded screening test appears to be a useful method for selecting patients in a pain-management program and warrants further investigation.

Water permeability of Necturus gallbladder epithelial cell membranes measured by nuclear magnetic resonance.

In order to assess the contribution of transcellular water flow to isosmotic fluid transport across Necturus gallbladder epithelium, we have measured the water permeability of the epithelial cell membranes using a nuclear magnetic resonance method. Spin-lattice (T1) relaxation of water protons in samples of gallbladder tissue where the extracellular fluid contained 10 to 20 mM Mn2+ showed two exponential components. The fraction of the total water population responsible for the slower of the two was 24 +/- 2%.

Circulating antibody-antigen complexes following Trypanosoma musculi infection in mice genetically selected to produce high or low affinity antibody.

Mice from lines genetically selected for the production of either high or low affinity antibody to protein antigens and which differ in their susceptibility to chronic immune complex disease were infected with Trypanosoma musculi. The parasite became patent in both lines by day 5 and no significant differences in the levels of parasites during the infection were observed between the two lines. Serum levels of both antigen non-specific and T.

Transepithelial transport of nonelectrolytes in the rabbit mandibular salivary gland.

The characteristics of nonelectrolyte secretion by the rabbit mandibular salivary gland have been investigated in an in vitro, perfused preparation. The concentrations of 14C-labeled nonelectrolytes were measured in saliva samples collected over a range of flow rates during the secretory response of the gland to continuous acetylcholine infusion. Of the nine nonelectrolytes studied, the two particularly lipid-soluble molecules, ethanol and antipyrine, appeared in the saliva at approximately the same concentration as in the perfusate, regardless of the secretory flow rate.

Determination of the affinity of antibodies to hepatitis B surface antigen in human sera.

The measurement of the affinity of anti-HBs antibody in human sera using 3 HBsAg-related antigens is described. The antigens used were (i) a synthetic linear peptide corresponding to amino acids 139-147 of the major polypeptide of HBsAg, (ii) a cyclical form of this same peptide and (iii) a polypeptide complex of a 28,000 MW glycoprotein and a 23,000 MW protein from purified HBsAg. The method was established with a pooled human anti-HBs immunoglobulin preparation and a monoclonal anti-HBs antibody reactive to the 'a' determinant of HBsAg.

Influence of antibody affinity on the performance of different antibody assays.

The effect of antibody affinity on the performance of 5 commonly used assays was studied. The assays used were measurement of antigen binding capacity in a Farr type assay, haemagglutination, solid-phase radioimmunoassay (SP-RIA), solid-phase ELISA and precipitation. The first 4 assays were all more sensitive for high affinity antibodies.

Glomerulonephritis induced by pre-formed immune complexes containing monoclonal antibodies of defined affinity and isotype.

The work presented here represents the first report of the induction of experimental immune complex (IC) disease in mice using monoclonal antibodies (MoAb) derived from somatic cell hybridization. IC were formed using two antigens of either high (DNP19BSA) or low (DNP4BSA) epitope density and five MoAb (four IgGl with varying affinities for the dinitrophenol hapten and one IgM with a similar affinity to that of the lowest affinity IgGl). Circulating levels and sizes of IC were dependent on the affinity of the antibody component of the complex.

Affinity of antibody responses in man to hepatitis B vaccine determined with synthetic peptides.

The affinity and level of antibody to hepatitis B surface antigen (anti-HBs) in recipients of a plasma-derived hepatitis B vaccine were determined with three different antigens. The first two antigens were prepared by chemical synthesis, to represent linear or cyclical forms of aminoacid sequences 139 to 147 of the major hepatitis B surface antigen (HBsAg) polypeptide. The binding of antibodies to these synthetic peptides was compared with that to a third antigen, prepared by solubilisation of the naturally occurring HBsAg, the basic component of the currently licensed hepatitis B vaccine in the United Kingdom.

Failure of affinity maturation leads to increased susceptibility to immune complex glomerulonephritis.

Mice, previously selected for the production of low affinity antibody after four injections of protein antigens in saline, fell into two groups on the basis of their antibody response after injection of adjuvantized antigen. One group produced antibody of sequentially rising affinity but the other produced only low affinity antibody. Mice from the latter group were interbred to produce low affinity non-maturing mice (low N/M mice).

Glomerulonephritis: the use of grafted hybridomas to investigate the role of epitope density, antibody affinity and antibody isotype in active serum sickness.

Two experimental models were used to investigate the role of antigen epitope density, antibody isotype and antibody affinity in immune-complex glomerulonephritis. In both models, two antigens were used: dinitrophenylated bovine serum albumin of high and low substitution ( DNP19BSA and DNP4BSA , respectively). In the first, acute actively induced model, a single intravenous injection of either of the two antigens was given to mice bearing hybridomas that secreted one of five monoclonal antibodies--four IgGl with varying affinities for the dinitrophenol hapten, and an IgM antibody with a similar affinity to that of the lowest affinity IgGl.

Hepatitis B surface antigen containing immune complexes occur in seronegative hepatocellular carcinoma patients.

IgG, IgM and hepatitis B surface antigen (HBsAg) containing immune complexes (IC) were detected by the Clq and conglutinin solid phase assays in both HBsAg+ and HBsAg- groups of patients with primary hepatocellular carcinoma (HCC). No differences were observed between the two patient groups either in the levels of antigen non-specific and HBsAg specific complexes or in the immunoglobulin isotype in the complexes. The results show that HBsAg can occur in an IC form in the sera of patients classified as HBsAg- by sensitive commercial assays and provides evidence of a further association of hepatitis B virus (HBV) and HCC in antigen negative patients.