Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine

Authors

Mark S. Riddle, Naval Medical Research Center
Robert W. Kaminski, Walter Reed Army Institute of Research
Carlos Williams, Naval Medical Research Center
Chad Porter, Naval Medical Research CenterFollow
Shahida Baqar, Naval Medical Research Center
Alexis Kordis, Walter Reed Army Institute of Research
Theron Gilliland, Naval Medical Research Center
Joyce Lapa, Naval Medical Research Center
Melissa Coughlin, Walter Reed Army Institute of Research
Chris Soltis, Walter Reed Army Medical Center
Erica Jones, Walter Reed Army Institute of Research
Jackie Saunders, Walter Reed Army Institute of Research
Paul B. Keiser, Walter Reed Army Institute of Research
Ryan T. Ranallo, Walter Reed Army Institute of Research
Robert Gormley, Naval Medical Research Center
Michael Nelson, Walter Reed Army Medical Center
K. Ross Turbyfill, Walter Reed Army Institute of Research
David Tribble, Uniformed Services University of the Health Sciences
Edwin V. Oaks, Walter Reed Army Institute of ResearchFollow

Date of this Version

2011

Comments

Published in Vaccine 29 (2011) 7009– 7019; doi:10.1016/j.vaccine.2011.07.033

Abstract

Background: Shigella flexneri 2a lipopolysaccharide 50 is a nasally delivered subunit vaccine consisting of a macromolecular complex composed of LPS, IpaB, IpaC and IpaD. The current study examined vaccine safety and immunogenicity across a dose range and the clinical performance of a new intranasal delivery device.

Methods: Volunteers (N = 36) were randomized to receive vaccine via the Dolphin^TM (Valois of America, Congers, New York) intranasal spray device at one of three doses (240, 480, and 690 μg) on days 0, 14, and 28. Another group (N = 8) received the 240 μg dose via pipette. Vaccine safety was actively monitored and antigen-specific humoral and mucosal immune responses were determined.

Results: There were no serious adverse events and the majority of adverse events (98%) were mild. Antibody secreting cells (ASC), plasma, and mucosal immune responses to Shigella antigens were detected at all three dose levels with the 690 μg dose inducing the highest magnitude and frequency of responses. Vaccination with comparable doses of Invaplex 50 via the Dolphin^TM resulted in higher plasma and ASC immune responses as compared to pipette delivery.

Conclusion: In this trial the S. flexneri 2a Invaplex 50 vaccine was safe, well-tolerated and induced robust levels of antigen-specific intestinal IgA and ASC responses. The spray device performed well and offered an advantage over pipette intranasal delivery.