Quantitative Determination of the Human Immune Response to Immunization with Meningococcal Vaccines

Abstract

A B S T R A C T Radioactive antigen binding tests have been developed to measure quantitatively the antibody response of 167 adults, 84 children, and 51 infants to several different preparations of group A and group C meningococcal polysaccharides. Almost all the adults injected responded and the geometric mean responses were approximately 15 /Ag/ml of antibody protein in individuals vaccinated subcutaneously with two preparations of group A vaccine. The geometric mean antibody concentration after immunization with two preparations of group C vaccine was approximately 35 Ag/ml. Most children aged 7 yr responded to immunization with two group A vaccines, and their mean response was only slightly less than that seen in adults. There was no difference between the subcutaneous and the intradermal route if both were given with jet gun. The majority of infants aged 6-13 months responded to a preparation of group A vaccine and the geometric mean titer was approximately 1.2 ug/ml. Adults, children, and infants responded significantly less to a preparation of group A polysaccharide which was of low molceular weight. INTRODUCTIONCurrently there are under development two meningococcal vaccines based upon the use of high molecular weight group-specific polysaccharides. Immunization of military recruits with the group C polysaccharide has been shown to be effective in preventing meningococcal disease (1), and in lowering the rate of acquisition of the nasopharyngeal carrier stage by group C meningococci (2). Such information has not yet been obtained for the group A vaccine, in part because these strains are exceedingly rare in the U. S. military population. The efficacy of this vaccine will probably need to be tested in the African "Meningitis belt" where disease is caused primarily by group A organisms (3).Received for publication 12 July 1971.Administration of either the group A or the group C vaccine to adults induces the formation of antibodies belonging to the three major immunoglobulin classes which have both bactericidal (4) and opsonic properties (5). To date quantitative data is available on the response of children.' There is no published data on the immune response of infants to these vaccines. Inasmuch as this age group stands to benefit most from meningococcal immunoprophylaxis (6), quantitative data of their serological response is vital.The present report will describe the immune response of adults, children, and infants to immunization with several preparations of meningococcal polysaccharides measured by means of quantitative radioactive antigen binding tests (7). METHODSAntigens. Group A meningococcal vaccines lots A-5, A-7, V-1, and group C meningococcal vaccines lots C-6 and C-7 were prepared as described by Gotschlich, Liu, and Artenstein (8). The group A polysaccharide contained in lots V-4 and V-5 was prepared by a modified procedure, employing cold phenol extraction to remove protein contamination.2 A-5 and C-6 were prepared at the Walter Reed Army Institute of Research; lots A-7 and C-7 by E. R. Squ...

Quantitative Measurement of “Natural” and Immunization-induced Haemophilus influenzas type b Capsular Polysaccharide Antibodies

“…Third, in contrast to the relatively constant level of anti-type b antibodies observed 3-4 years after immunization of the adults, a decline from the maximum level of serum antibodies was observed in most of the infants and children within several months. Similar results were recently observed for infants and adults receiving injections of the meningococcal group C polysaccharide [10] and for infants and children receiving injection of whole encapsulated Diplococcus pneumoniae types I and VI and Salmonellae [14,32].…”

“…Two milliliters of H. influenzae type b (strain "Rab") polysaccharide (5.0 mg/ml) [10], were brought to pH 10.0 with constant stirring. Cyanogen bromide (50 mg/ml H 2 O) [36] was added (0.1 mg CNBr/mg polysaccharide) and the pH maintained at 10.0 with 0.1 N NaOH for 1 hr at room temperature by addition of 0.1 N NaOH.…”

“…influenzae type b capsular polysaccharide, prepared by a modification of a previously published method [10], was dissolved in phosphate-buffered saline or precipitated from 0.05 M sodium acetate on 2 mg aluminum hydroxide.…”

Quantitative determination of antibody to capsular polysaccharide in infection with type III strains of group B Streptococcus.

“…In this investigation, the RABA was standardized by reference to antisera with known content of precipitating antibody. The degree of antigen binding was converted to antibody concentration with full recognition of the possible errors resulting from this conversion (16). The method of least (24).…”

“…Organisms were grown in Todd-Hewitt broth modified with additional quantities of disodium phosphate and glucose (12 Farr (17), and modified by several investigators for the detection of antibody to the capsular polysaccharides of numerous organisms, was employed (16,18,19). This method has been described in detail previously (11).…”