HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Capozzo, A. V. E. Articles by Pasetti, M. F. Search for Related Content PubMed PubMed Citation Articles by Capozzo, A. V. E. Articles by Pasetti, M. F.

Neonatal Immunization with a Sindbis Virus-DNA Measles Vaccine Induces Adult-Like Neutralizing Antibodies and Cell-Mediated Immunity in the Presence of Maternal Antibodies¹

Alejandra V. E. Capozzo^2,*, Karina Ramírez^*, John M. Polo, Jeffrey Ulmer, Eileen M. Barry^*, Myron M. Levine^* and Marcela F. Pasetti^3,*

^* Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD 21201; and Chiron Vaccines, Emeryville, CA 94608

Infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal Abs that interfere with successful immunization. We evaluated the immune responses elicited by Sindbis virus replicon-based DNA vaccines encoding measles virus (MV) hemagglutinin (H, pMSIN-H) or both hemagglutinin and fusion (F, pMSINH-FdU) glycoproteins in neonatal mice born to naive and measles-immune mothers. Despite the presence of high levels of maternal Abs, neonatal immunization with pMSIN-H induced long-lasting, high-avidity MV plaque reduction neutralization (PRN) Abs, mainly IgG2a, that also inhibited syncytium formation in CD150⁺ B95-8 cells. IgG secreting plasma cells were detected in spleen and bone marrow. Newborns vaccinated with pMSINH-FdU elicited PRN titers that surpassed the protective level (200 mIU/ml) but were short-lived, had low syncytium inhibition capacity, and lacked avidity maturation. This vaccine failed to induce significant PRN titers in the presence of placentally transferred Abs. Both pMSIN-H and pMSINH-FdU elicited strong Th1 type cell-mediated immunity, measured by T cell proliferation and IFN- production, that was unaffected by maternal Abs. Newborns responded to measles DNA vaccines with similar or even higher PRN titers and cell-mediated immunity than adult mice. This study is the first demonstration that a Sindbis virus-based measles DNA vaccine can elicit robust MV immunity in neonates bypassing maternal Abs. Such a vaccine could be followed by the current live attenuated MV vaccine in a heterologous prime-boost to protect against measles early in life.

This article has been cited by other articles:

				C.-H. Pan, N. Nair, R. J. Adams, M. C. Zink, E.-Y. Lee, F. P. Polack, M. Singh, D. T. O'Hagan, and D. E. Griffin Dose-Dependent Protection against or Exacerbation of Disease by a Polylactide Glycolide Microparticle-Adsorbed, Alphavirus-Based Measles Virus DNA Vaccine in Rhesus Macaques Clin. Vaccine Immunol., April 1, 2008; 15(4): 697 - 706. [Abstract] [Full Text] [PDF]

				L. J. White, M. M. Parsons, A. C. Whitmore, B. M. Williams, A. de Silva, and R. E. Johnston An Immunogenic and Protective Alphavirus Replicon Particle-Based Dengue Vaccine Overcomes Maternal Antibody Interference in Weanling Mice J. Virol., October 1, 2007; 81(19): 10329 - 10339. [Abstract] [Full Text] [PDF]