NDLI: Use of a tuberculin purified protein derivative--Asn-Ala-Asn-Pro conjugate in bacillus Calmette-Guérin primed mice overcomes H-2 restriction of the antibody response and avoids the need for adjuvants.

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Use of a tuberculin purified protein derivative--Asn-Ala-Asn-Pro conjugate in bacillus Calmette-Guérin primed mice overcomes H-2 restriction of the antibody response and avoids the need for adjuvants.

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Use of a tuberculin purified protein derivative--Asn-Ala-Asn-Pro conjugate in bacillus Calmette-Guérin primed mice overcomes H-2 restriction of the antibody response and avoids the need for adjuvants.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lussow, A. R. Lambert, P. H. Rénia, L. Mazier, D. Verhave, J. P. Verdini, A. S. Pessi, A. Louis, J. A. Del Giudice, G.
Description	Author Affiliation: Lussow AR ( Department of Pathology, University of Geneva, Switzerland.);
Abstract	Because of its immunodominancy, and because it is conserved in different geographical isolates of Plasmodium falciparum, the repetitive sequence of the circumsporozoite protein, (Asn-Ala-Asn-Pro)n [(NANP)n], has been envisaged for the development of an anti-falciparum malaria subunit vaccine. However, the murine immune response to (NANP)n peptides, either carrier-free or coupled to carrier proteins, was shown to be inducible only by using strong (e.g., Freund's) adjuvants. Furthermore, response to the carrier-free peptide, administered in adjuvant, is genetically restricted to I-Ab mice. In the present paper, we report that high titers of antibodies against the NANP repetitive epitope were obtained in responder C57BL/6 (H-2b) mice when they were primed with live BCG (bacillus Calmette-Guérin Mycobacterium tuberculosis var. bovis) and immunized once with the synthetic peptide (NANP)40 coupled to tuberculin purified protein derivative (PPD) without the use of any adjuvant. This approach also led to the production of high titers of anti-NANP antibodies in ASW (H-2s), B10.RIII (H-2r), BALB/c (H-2d), C3H/He (H-2k), and DBA/1 (H-2q) nonresponder mice after two injections of the conjugate. In both cases, BCG priming was obligatory for the induction of antibodies reacting with the synthetic peptide. The levels of anti-NANP antibodies in nonresponder BALB/c mice were demonstrated to be comparable to the levels induced after PPD-(NANP)40 immunization in Freund's complete or incomplete adjuvant. The antibodies induced were also capable of recognizing P. falciparum sporozoites in immunofluorescence assays and, furthermore, these antibodies inhibited the penetration of live sporozoites into human hepatocytes in vitro. This system functioned independently of the subjects' resistance or susceptibility to BCG infection. Given the widespread natural exposure to mycobacterial antigens and the extensive use of BCG and PPD in the human population, this approach might be envisaged for vaccination with malaria peptides.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	8
Volume Number	87
Language	English
Publisher	National Academy of Sciences
Publisher Date	1990-05-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Antibody Formation Antigens, Protozoan Immunology BCG Vaccine H-2 Antigens Protozoan Proteins Amino Acid Sequence Animals Administration & Dosage Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Inbred Strains Molecular Sequence Data Mycobacterium Bovis Plasmodium Falciparum Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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