Immunogenicity of recombinant Modified Vaccinia Ankara following a single or multi-dose vaccine regimen in rhesus monkeys |
| |
Authors: | Lauren E. Grandpre Jonathan S. Duke-Cohan Bonnie A. Ewald Colleen Devoy Dan H. Barouch Norman L. Letvin Ellis L. Reinherz Lindsey R. Baden Raphael Dolin Michael S. Seaman |
| |
Affiliation: | 1. Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States;2. Laboratory of Immunobiology and Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, United States;3. Division of Infectious Diseases, Brigham & Women''s Hospital, Boston, MA 02115, United States;4. Department of Medicine, Harvard Medical School, Boston, MA 02115, United States |
| |
Abstract: | Modified Vaccinia Ankara (MVA) is a replication-defective strain of vaccinia virus (VV) that is being investigated in humans as an alternative vaccine against smallpox. Understanding the parameters of a MVA vaccine regimen that can effectively enhance protective immunity will be important for clinical development. The present studies utilize cohorts of rhesus monkeys immunized with recombinant MVA (rMVA) or recombinant VV (rVV) vaccine vectors to investigate the magnitude, breadth, and durability of anti-VV immunity elicited by a single or multi-dose vaccine regimen. These data demonstrate that a single immunization with rMVA elicits weaker cellular and humoral immunity compared to a single inoculation with rVV. However, vaccine-elicited antibody responses, but not T cell responses, are significantly enhanced with repeated immunizations of rMVA. Importantly, only monkeys receiving up to four inoculations with rMVA generated neutralizing antibody (NAb) responses that were comparable in magnitude and durability to those elicited in monkeys receiving two inoculations with rVV. These data also show that the breadth of antibody responses against protein antigens associated with two antigenically distinct forms of infectious VV are similar in rMVA- and rVV-immunized monkeys. Together, these studies suggest that a multi-dose vaccine regimen utilizing up to four inoculations of MVA generates robust and durable antibody-mediated immunity comparable to that elicited by replication-competent VV. |
| |
Keywords: | MVA Vaccinia virus Vaccine Neutralizing antibody Rhesus monkey |
本文献已被 ScienceDirect 等数据库收录! |
|