Heterologous Prime-Boost Immunizations with a Virosomal and an Alphavirus Replicon Vaccine

Mateusz Walczak, Arjan de Mare, Annelies Riezebos-Brilman, Joke Regts, Baukje-Nynke Hoogeboom, Jeroen T. Visser, Marc Fiedler, Pidder Jansen-Duerr, Ate G. J. van der Zee, Hans W. Nijman, Jan Wilschut, Toos Daemen*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

19 Citaten (Scopus)

Samenvatting

Heterologous prime-boost immunization strategies in general establish higher frequencies of antigen-specific T lymphocytes than homologous prime-boost protocols or single immunizations. We developed virosomes and recombinant Semliki Forest virus (rSFV) as antigen delivery systems, each capable of inducing strong CTL responses in homologous prime-boost protocols. Here, we demonstrate that a heterologous prime-boost with recombinant Semliki Forest virus (rSFV) encoding;a fusion protein of E6 and E7 of human papillomavirus (HPV) type 16 and virosomes containing the HPV16 E7 protein resulted in higher numbers of antigen-specific CTL in mice than homologous protocols. Evasion of vector-specific immunity appeared to play a role in establishing these high frequencies, as coinduction of vector-specific responses during the prime immunization reduced 1:he frequency of antigen-specific CTL after a heterologous booster. However, the high numbers of CTL initially primed by the heterologous protocols did not correlate with enhanced responsiveness to in vitro antigenic stimulation, nor in improved cytolytic activity or antitumor responses in vivo compared to a homologous protocol with rSFV. This lack of correlation could not be explained by changes in numbers of regulatory T cells. However, we observed differences in the frequencies of T cell subsets within the E7-specific CD8(+) T cell population, e.g. higher frequencies of central memory T cells upon homologous immunizations compared to heterologous immunizations. The induction of central memory T cells is crucial for a cancer vaccine as these cells are known to rapidly expand.Jpon recall stimulation. This study demonstrates that the strongly increased number of antigen-specific CTL as induced by heterologous prime-boost immunizations, often used as a proof for the enhanced efficacy of such regimes, does not necessarily equal superior functional antitumor responses.

Originele taal-2English
Pagina's (van-tot)65-77
Aantal pagina's13
TijdschriftMolecular pharmaceutics
Volume8
Nummer van het tijdschrift1
DOI's
StatusPublished - 2011

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