The Relative Significance of Graded Immunizing and Challenge Doses in Measuring the Potency of Vaccines

Batson, H. C.

doi:10.1084/jem.90.3.233

Cited by 6 publications

(4 citation statements)

References 10 publications

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“…In the active mouse protection test, carried out with a constant challenge and graded immunizing doses (Batson, 1949), good protection was obtained by vaccination with one subcutaneous injection of the chrome vaccine stored at 4-6' C. As regards mouse-protection tests, it was considered by Felix (1941) that active immunization experiments in mice do not disclose those great differences in the antigenic value of various preparations of the Vi-antigen, which are so clearly demonstrated by using the serum of vaccinated rabbits or horses in passive protection experiments with mice, or even by in vitro laboratory tests. Ando & Nakamura (1950) disagree with this opinion and state, 'In our experiments the mouse-method without using mucin, if ED 50 (the average immunizing dose) is determined against a certain challenge dose, is shown to be sensitive enough for determining the immunizing power of vaccines.…”

Section: Discussionmentioning

confidence: 99%

Chrome typhoid vaccine

Vella

1963

J. Hyg.

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1. Experimental typhoid vaccines, treated by 1% formalin and 0·02% chrome alum (KCr(SO4)2.12H2O), as suggested by Japanese workers were prepared and tested by the usual in vitro and in vivo tests.2. Agglutination tests, antibody production in rabbits, active and passive mouse protection tests confirm the stability of the Vi antigen of the vaccine, if properly stored, and the good protection afforded to laboratory animals in both the active and passive mouse protection tests.3. It is suggested that only a full-scale field trial in a typhoid endemic area can give the answer as to the real efficacy and/or superiority of the chrome vaccine over other typhoid vaccines.

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Section: Discussionmentioning

confidence: 99%

Chrome typhoid vaccine

Vella

1963

J. Hyg.

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“…This vaccine was prepared in the same manner as are all lots of triple typhoid vaccine produced at the Army Medical Service Graduate School (12,23). 1 A monovalent reference standard vaccine also has been prepared in a similar manner except for omission of the paratyphoid components. This vaccine is used as the reference in assays on experimental monovalent vaccines but, as stated previously, the data available fail to provide any evidence of a consistent difference in protective potency against S. typhosa challenge of the monovalent and triple typhoid reference vaccines.…”

Section: The Reference Standard Vaccinementioning

confidence: 99%

“…Estimation of relative potency is accomplished by means of the following equation: (1) Potency as percent of standard=antilog (2+±)…”

Section: Relative Potencymentioning

confidence: 99%

Mouse-Protective Potency Assay of Typhoid Vaccine: As Performed at the Army Medical Service Graduate School

Batson¹,

Brown²,

Oberstein³

1951

Public Health Reports (1896-1970)

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The need for an efficient, practical laboratory method for determining the potency of tvphoid vaccines long has been recognized by immunologists concerned with the development, production, and assay of the product. The need in relation to production and control in routine manufacture of typhoid vaccine is mainly for a testing method which will permit the ready demonstration that an individual lot, or successive lots, of vaccine equal or exceed an established level of potency. Researchers, on the other hand, require an assay method which, in addition to the foregoing, permits quantitative estimation of potency, i. e., which permits numerical expression of potency in absolute or relative terms with an estimable degree of uncertainty. Only by the use of such a method is the investigator enabled to detect or evaluate differences or changes in potency as effected by experimental treatments or conditions of interest. Methods early used in the determination of the potency of typhoid vaccines were based upon parenteral administration of the products to rabbits and subsequent in viro determination of the agglutinin response (15), or the actual protection of such immunized rabbits against subacute infection following injection of living, virulent Salmonella typhosa (18). It is beyond the scope of this report to discuss or criticize these tests in detail and it is considered sufficient to state that such methods have proved to be neither adequately definitive nor reproducible to warrant their continued use. Investigation and establishment by Siler and his associates at the Army Medical School (22) of the mouse-protection test for assessing the antibody response of humaDs to typhoid immunization stimulated

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“…vacdues prepared from strains 58 and 58V were compared directly in one assay, while vaccines from strains 58B and 58A were compared in another. The assay procedure employed was based on the use of graded doses of vaccine and a constant challenge dose of viable S. typhosa suspended in 5 per cent mucin since a previous study (12) indicated that use of this method permits comparisons of greater precision than are obtained by procedures more commonly employed (13,14). The mice employed in these assays were 15 to 17 gin., male, white Swiss mice (CFW strain).…”

Section: Mouse-protection Potency Testsmentioning

confidence: 99%

The Virulence and Immunogenicity of Strains Derived From Salmonella Typhosa 58 (Panama Carrier)

Batson¹,

Landy²,

Brown³

1950

Journal of Experimental Medicine

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Since the early days of immunology, it has been considered that high virulence and recency of isolation from pathological material were essential attributes of strains of bacteria to be used in production of superior immunizing agents. In spite of a surprising paucity of supporting factual information this concept has pesisted.Perhaps in no field of investigative immunology has the theory of an essential relationship of virulence to immunogenicity been accepted more widely than it has been in relation to the development of immunizing agents against typhoid. As early as 1910, Leishman (1) pointed out that employment of highly virulent cultures of Salmonella typhosa appeared to have certain theoretical advantages in the preparation of typhoid vaccines. Perry, Findlay, and Bensted (2), who employed active-immunity protection tests on mice, concluded that the more highly virulent the strains of S.typhosa employed in preparing vaccines, the greater was the immunizing activity of the resultant products. Similar conclusions were reached by Arkwright (3), Grinnell (4), and Brown (5). In many of these earlier investigations, however, virulence and avimlence was not dearly distinguished from smooth-rough variation of strains; in fact, virulence and smoothness (also avirulence and roughness) generally were considered essentially synonymous.One of the most comprehensive studies of the relationship of virulence to antigenicity of S. typhosa cultures was conducted by Siler and his associates at the Army Medical School (6). This investigation included a study of seven strains of varied virulence and it was found that, as measured by active-immunity mouse-protection tests and by "0" agglutinin and mouse-protective antibody responses in human volunteers, vaccines prepared from virulent strains were more highly immunogenic than were those prepared from avirulent strains.Felix (7) likewise reported that highly virulent strains of S. typhosa exhibited the greatest immunizing activity. He placed major emphasis on the r61e played by Vi antigen both in virulence and in immunogenicity. There is, however, no unanimity of opinion in regard to any essential relationship between virulence and immunogenicity. This is evidenced more by the development of certain immunizing agents and methods than by any specific investigations of the phenomenon itself. It is not difficult to understand why there is no unanimity of opinion in regard to the supposed mutual interdependent relationship of virulence and immunogenicity since there has been a marked lack of uniformity in the experimental techniques employed in the various investigations and most of the published

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The Relative Significance of Graded Immunizing and Challenge Doses in Measuring the Potency of Vaccines

Cited by 6 publications

References 10 publications

Chrome typhoid vaccine

Chrome typhoid vaccine

Mouse-Protective Potency Assay of Typhoid Vaccine: As Performed at the Army Medical Service Graduate School

The Virulence and Immunogenicity of Strains Derived From Salmonella Typhosa 58 (Panama Carrier)

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