The theory proposed is that a critical level of specific serum IgG is sufficient to confer protection against infectious diseases by inactivating the inoculum of the pathogen. This theory relies heavily on evaluation of licensed vaccines and includes the following: Measurement of serum antibodies only reliably predicts the efficacy of vaccines, according to regulatory agencies. Serum IgG antibodies alone account for the protection conferred by passive immunization. "Herd" immunity conferred by vaccines on viral and bacterial diseases is best explained by serum antibodies that inactivate the inoculum on mucosal surfaces, thus reducing the pathogen's transmission. Once the disease is manifest, serum antibodies induced by active immunization will neither relieve symptoms nor eliminate the pathogen; specific IgG must be present when the host encounters the pathogen in order to confer protective immunity. Information about the initial pathogen-host contact is vital, whereas knowledge of the symptomatology of the disease may not be essential for vaccine development.

https://www.jstor.org/stable/info/30135444

Perspective: Hypothesis: Serum IgG Antibody Is Sufficient to Confer Protection against Infectious Diseases by Inactivating the Inoculum

Background Despite recent progress in understanding the molecular basis of Vibrio cholerae pathogenesis, there is relatively little knowledge of the factors that determine the variability in human susceptibility to V. cholerae infection. Methods and findings We performed an observational study of a cohort of household contacts of cholera patients in Bangladesh, and compared the baseline characteristics of household members who went on to develop culture-positive V. cholerae infection with individuals who did not develop infection. Although the vibriocidal antibody is the only previously described immunologic marker associated with protection from V. cholerae infection, we found that levels of serum IgA specific to three V. cholerae antigens-the B subunit of cholera toxin, lipopolysaccharide, and TcpA, the major component of the toxin-co-regulated pilus-also predicted protection in household contacts of patients infected with V. cholerae O1, the current predominant cause of cholera. Circulating IgA antibodies to TcpA were also associated with protection from V. cholerae O139 infection. In contrast, there was no association between serum IgG antibodies specific to these three antigens and protection from infection with either serogroup. We also found evidence that host genetic characteristics and serum retinol levels modify susceptibility to V. cholerae infection. Conclusions Our observation that levels of serum IgA (but not serum IgG) directed at certain V. cholerae antigens are associated with protection from infection underscores the need to better understand anti-V. cholerae immunity at the mucosal surface. Furthermore, our data suggest that susceptibility to V. cholerae infection is determined by a combination of immunologic, nutritional, and genetic characteristics; additional factors that influence susceptibility to cholera remain unidentified.

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Susceptibility to Vibrio cholerae Infection in a Cohort of Household Contacts of Patients with Cholera in Bangladesh

ALTHOUGH vaccination has assisted the control of many bacterial diseases, parenteral vaccination against enteric disease is not as satisfactory as we could wish1. This is attributable to incomplete knowledge of both the pathogenesis of intestinal infections and the protective immune responses of the alimentary tract, with the result that vaccine development has been largely empirical. New knowledge of the specific determinants of microbial pathogenicity2 provides a sounder basis for the development of effective vaccines and the following report is an example of this approach to disease control.

Protection against enteric disease caused by Escherichia coli--a model for vaccination with a virulence determinant?

The survival rate, p , of a measured inoculum of Staph. aureus in a standard volume of denbrinated blood, is a reliable quantitative measure of the bactericidal power of blood. The number of viable organisms in the inoculum and in the blood-bacterium mixture may be estimated with the necessary accuracy by counts of colonies developing from measured volumes of the fluids let fall on to the surface of solid media. Fildes' agar was the most suitable medium for this surface-viable count, and was selected on the basis of four criteria; of the media tested it yielded the highest counts, and the counts conformed most closely to a Poisson series; and on it the mean colony size was maximum, and the coefficient of variation of colony size was minimum. On this medium, the close conformity of the separate count values to a Poisson series enabled the standard error of the survival rate to be determined from a simplification of the general expression for the standard error of a ratio. The number of colonies growing from a sample of a blood-bacterium mixture may be reduced, not by killing of the individual cocci, but as a result of their aggregation either by agglutinins in the blood, or in the cytoplasm of leucocytes that are phagocytic but not bactericidal. It appears that these mechanisms are unlikely to operate in blood-bacterium mixture containing relatively few organisms; in such mixtures the survival rate is a reflexion of the killing power only. The immunological significance of p has not been investigated, but the range of values for healthy human adults differs significantly from that for sufferers from chronic staphylococcal infection. Moreover, by the technique employed differences may be detected between individual values of p that cannot reasonably be attributed to technical or sampling errors.

The Estimation of the Bactericidal Power of the Blood. With a Note by J. O. IRWIN.

Subcutaneous immunization of rabbits with a combination of Vibrio cholerae lipopolysaccharide (LPS) and enterotoxin induced a more than 100-fold-higher degree of protection against intestinal challenge with live cholera vibrios than did vaccination with either of the two antigens alone. Such a synergistic effect was also obtained by immunization with a combination of LPS and choleragenoid. The immunization with LPS and toxin (or toxoid) in combination did not enhance the reistance to toxin challenge above that induced by the toxin component alone. This, together with data from titrations of anti-LPS and antitoxin antibodies in serum and in intestinal washings, contradicts enhanced immune responses due to adjuvant action of the two antigens as the explanation for the synergistic effect of the combined vaccines. A more likely explanation would be that the antibacterial and antitoxic immune responses, without being increased in themselves, function synergistically by interfering with two separate events in cholera pathogensis.

Synergistic protective effect in rabbits of immunization with Vibrio cholerae lipopolysaccharide and toxin/toxoid.

Research in cholera has been greatly hampered by the lack of a clearly correlated model of infection in any experimental animal. The value of various cholera vaccines must, at the moment, be assessed by expensive and prolonged clinical trials in those climatically difficult areas of the world where the disease is endemic. Recent field trials conducted in the Matlab Bazaar area of East Pakistan [1-7] have indicated that there is a clear correlation be-

The antigens of Vibrio cholerae involved in the vibriocidal action of antibody and complement.

Some correlation was found between antibody titers measured by in-vitro techniques and protection in infant mice. At least three types of protective antibodies, which corresponded to antilipopolysaccharide, antiprotein, and anticholeragen, were present. Strong cross-protection was evident with the various antisera against Inaba and Ogawa organisms. The antibodies responsible for this cross-protection against serotypes of Vibrio cholerae were shown to be directed against common polysaccharide antigen(s), common protein determinant(s), and enterotoxin. Antibodies present at the site of infection were more effective in protecting infant mice from fatal infection than serum antibodies.

Sim Hee Neoh

Papers

The antigens of Vibrio cholerae involved in the vibriocidal action of antibody and complement.

Protection of Infant Mice against Cholera by Antibodies to Three Antigens of Vibrio cholerae

Quantitative assay of a protein antigen of Vibrio cholerae involved in the vibriocidal action of antibody and complement.