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Infection and Immunity, September 2005, p. 5835-5841, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5835-5841.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Combined Conjugate Vaccines: Enhanced Immunogenicity with the N19 Polyepitope as a Carrier Protein

Karin Baraldo,1 Elena Mori,1 Antonella Bartoloni,2 Francesco Norelli,2 Guido Grandi,1 Rino Rappuoli,1 Oretta Finco,1 and Giuseppe Del Giudice1*

Research Center,1 Technology Development, Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy2

Received 25 March 2005/ Returned for modification 11 April 2005/ Accepted 12 May 2005

The N19 polyepitope, consisting of a sequential string of universal human CD4+-T-cell epitopes, was tested as a carrier protein in a formulation of combined glycoconjugate vaccines containing the capsular polysaccharides (PSs) of Neisseria meningitidis serogroups A, C, W-135, and Y. Good antibody responses to all four polysaccharides were induced by one single immunization of mice with N19-based conjugates. Two immunizations with N19 conjugates elicited anti-MenACWY antibody titers comparable to those induced after three doses of glycoconjugates containing CRM197 as carrier protein. Compared to cross-reacting material (CRM)-based constructs, lower amounts of N19-MenACWY conjugates still induced high bactericidal titers to all four PSs. Moreover, N19-MenACWY-conjugated constructs induced faster and higher antibody avidity maturation against meningococcal C PS than CRM-based conjugates. Very importantly, N19-specific antibodies did not cross-react with the parent protein from which N19 epitopes were derived, e.g., tetanus toxoid and influenza virus hemagglutinin. Finally, T helper epitopes of the N19 carrier protein were effectively generated both in vivo (after immunization with the N19 itself) and in vitro (after restimulation of epitope-specific spleen cells). Taken together, these data show that the N19 polyepitope represents a strong and valid option for the generation of improved or new combined glycoconjugate vaccines.

* Corresponding author. Mailing address: Research Center, Chiron Vaccines, via Fiorentina 1, 53100 Siena, Italy. Phone: 39-0577-243261. Fax: 39-0577-243564. E-mail: giuseppe_del_giudice{at}chiron.com.

Editor: D. L. Burns

Infection and Immunity, September 2005, p. 5835-5841, Vol. 73, No. 9
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.9.5835-5841.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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