A recombinant vaccine expressed in the milk of transgenic mice protects Aotus monkeys from a lethal challenge with Plasmodium falciparum
| Autor: | Louis H. Miller, Harry M. Meade, Anthony W. Stowers, Lanling Zou, Lynn Lambert, Michael C. Kennedy, Allan Saul, Li-How Chen, David C. Kaslow, Carole A. Long, Yanling Zhang, Timothy J. Rice |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Glycosylation
Time Factors medicine.drug_class medicine.medical_treatment Molecular Sequence Data Plasmodium falciparum Antibodies Protozoan Mice Transgenic Biology Monoclonal antibody law.invention Mice chemistry.chemical_compound Antigen law Malaria Vaccines parasitic diseases Vaccines DNA medicine Animals Amino Acid Sequence Antigens Malaria Falciparum Multidisciplinary Malaria vaccine Biological Sciences biology.organism_classification Virology Recombinant Proteins Protein Structure Tertiary Vaccination Milk chemistry Aotus trivirgatus Recombinant DNA Adjuvant |
| Zdroj: | Proceedings of the National Academy of Sciences. 99:339-344 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.012590199 |
| Popis: | Two strains of transgenic mice have been generated that secrete into their milk a malaria vaccine candidate, the 42-kDa C-terminal portion of Plasmodium falciparum merozoite surface protein 1 (MSP1 42 ). One strain secretes an MSP1 42 with an amino acid sequence homologous to that of the FVO parasite line, the other an MSP1 42 where two putative N-linked glycosylation sites in the FVO sequence have been removed. Both forms of MSP1 42 were purified from whole milk to greater than 91% homogeneity at high yields. Both proteins are recognized by a panel of monoclonal antibodies and have identical N termini, but are clearly distinguishable by some biochemical properties. These two antigens were each emulsified with Freund's adjuvant and used to vaccinate Aotus nancymai monkeys, before challenge with the homologous P. falciparum FVO parasite line. Vaccination with a positive control molecule, a glycosylated form of MSP1 42 produced in the baculovirus expression system, successfully protected five of six monkeys. By contrast, vaccination with the glycosylated version of milk-derived MSP1 42 conferred no protection compared with an adjuvant control. Vaccination with the nonglycosylated, milk-derived MSP1 42 successfully protected the monkeys, with 4/5 animals able to control an otherwise lethal infection with P. falciparum compared with 1/7 control animals. Analysis of the different vaccines used suggested that the differing nature of the glycosylation patterns may have played a critical role in determining efficacy. This study demonstrates the potential for producing efficacious malarial vaccines in transgenic animals. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|