Rapid and long-term immunity elicited by DNA encoded antibody prophylaxis and DNA vaccination against Chikungunya virus

Autor(es): Muthumani Karuppiah, Block Peter, Flingai Seleeke, Muruganantham Nagarajan, Chaaithanya Itta Krishna, Tingey Colleen, Wise Megan, Reuschel Emma L, Chung Christopher, Muthumani Abirami, Sarangan Gopalsamy, Srikanth Padma, Khan Amir S, Vijayachari Paluru, Sardesai Niranjan Y, Kim J Joseph, Ugen Kenneth E, Weiner David B


Resumo: Vaccination - passive antibody therapies are critical for controlling infectious diseases. Passive antibody administration has limitations including the necessity for purification - the delivery of multiple injections required for efficacy. Vaccination is associated with a lag phase before generation of immunity. Novel approaches reported here utilize the benefits of both methods for the rapid generation of effective immunity. An antibody-based prophylaxis/therapy entailing the electroporation-mediated delivery of synthetic plasmids, encoding biologically active anti-Chikungunya virus envelope mAb (designated dMAb), was designed - evaluated for anti-viral efficacy as well as for the ability to overcome shortcomings inherent with conventional active vaccination by a novel passive immune-based strategy. One intramuscular injection of the CHIKV-dMAb produced antibodies in vivo more rapidly than active vaccination with a CHIKV-DNA vaccine. This dMAb neutralized diverse CHIKV clinical isolates - protected mice from viral challenge. Combinations of both afford rapid as well as long-lived protection. We report that a DNA based dMAb strategy induces rapid protection against an emerging viral infection, which can be combined with DNA vaccination providing a uniquely both short term - long-term protection against this emerging infectious disease. These studies have implications for pathogen treatment - control strategies.


Palavras-Chave: DNA plasmid; Chikungunya virus; dMAb; Monoclonal antibody; Passive antibody prophylaxis and therapy


Imprenta: The Journal of Infectious Diseases, v. 214, n. 3, p. 369-378, 2016


Identificador do objeto digital: 10.1093/infdis/jiw111


Descritores: Chikungunya virus - Cytopathology ; Chikungunya virus - DNA ; Chikungunya virus - Antibodies ; Chikungunya virus - Infectious diseases ; Chikungunya virus - Viral infections ; Chikungunya virus - Molecular methods ; Chikungunya Virus - Virus ; Chikungunya virus - Vaccine


Data de publicação: 2016