Poor Immune Responses of Newborn Rhesus Macaques to Measles Virus DNA Vaccines Expressing the Hemagglutinin and Fusion Glycoproteins

• Type of Material: Article
• Authors: Fernando P. Polack, Johns Hopkins University; Shari L. Lydy, Emory University; Sok-Hyong Lee, Johns Hopkins University; Paul Rota, Emory University; William J. Bellini, Centers for Disease Control and Prevention; Robert J. Adams, Johns Hopkins University; Harriet Robinson, Emory University; Diane E. Griffin, Johns Hopkins University
• Language: English
• Date: 2013-02-01
• Publisher: American Society for Microbiology
• Publication Version: Final Published Version
• Copyright Statement: © 2013, American Society for Microbiology. All Rights Reserved.
• Final Published Version (URL): http://dx.doi.org/10.1128/CVI.00394-12
• Title of Journal or Parent Work: Clinical and Vaccine Immunology
• ISSN: 1556-6811
• Volume: 20
• Issue: 2
• Start Page: 205
• End Page: 210
• Grant/Funding Information: This research was supported by research grants from The Bill and Melinda Gates Foundation, the National Institutes of Health (R01 AI35149), and the Centers for Disease Control and Prevention (PA99066).
• Keywords: INFECTIOUS DISEASES; IFN-GAMMA; Science & Technology; MICROBIOLOGY; MATERNAL ANTIBODY; INFANTS; NEUTRALIZING ANTIBODY; Immunology; Life Sciences & Biomedicine; IMMUNOLOGY; ATYPICAL MEASLES; Microbiology; PROTECTION; INFECTION; HUMORAL-IMMUNE; Infectious Diseases; VACCINATION; T-LYMPHOCYTES
• Research Categories: Biology, Microbiology; Health Sciences, Pathology

Abstract

A vaccine that would protect young infants against measles could facilitate elimination efforts and decrease morbidity and mortality in developing countries. However, immaturity of the immune system is an important obstacle to the development of such a vaccine. In this study, DNA vaccines expressing the measles virus (MeV) hemagglutinin (H) protein or H and fusion (F) proteins, previously shown to protect juvenile macaques, were used to immunize groups of 4 newborn rhesus macaques. Monkeys were inoculated intradermally with 200 μg of each DNA at birth and at 10 months of age. As controls, 2 newborn macaques were similarly vaccinated with DNA encoding the influenza virus H5, and 4 received one dose of the current live attenuated MeV vaccine (LAV) intramuscularly. All monkeys were monitored for development of MeV-specific neutralizing and binding IgG antibody and cytotoxic T lymphocyte (CTL) responses. These responses were poor compared to the responses induced by LAV. At 18 months of age, all monkeys were challenged intratracheally with a wild-type strain of MeV. Monkeys that received the DNA vaccine encoding H and F, but not H alone, were primed for an MeV-specific CD8+ CTL response but not for production of antibody. LAV-vaccinated monkeys were protected from rash and viremia, while DNA-vaccinated monkeys developed rashes, similar to control monkeys, but had 10-fold lower levels of viremia. We conclude that vaccination of infant macaques with DNA encoding MeV H and F provided only partial protection from MeV infection. Copyright © 2013, American Society for Microbiology. All Rights Reserved.