Increased immunogenicity of recombinant Ad35-based malaria vaccine through formulation with aluminium phosphate

Olga J A E Ophorst1, Katarina Radosević, Jaco M Klap

  • 1Crucell Holland BV, P.O. Box 2048, 2301 CA Leiden, The Netherlands. o.ophorst@Crucell.com

Vaccine
|July 25, 2007
PubMed

Insights

Formulating recombinant Adenovirus serotype 35 (rAd35) malaria vaccines with aluminium phosphate adjuvant (AlPO(4)) significantly boosted immune responses. This approach enhances T and B cell activity for a more potent malaria vaccine candidate.

Area of Science:

  • * Virology and Immunology
  • * Vaccine Development
  • * Parasitic Diseases

Background:

  • * Recombinant Adenovirus serotype 35 (rAd35) viral vaccines show promise for inducing immune responses against Plasmodium parasite circumsporozoite protein (CS).
  • * Optimizing immunogenicity is crucial for developing effective malaria vaccines.
  • * Conventional protein-based vaccines often utilize adjuvants, but their compatibility with viral vectors needs careful consideration.

Purpose of the Study:

  • * To evaluate the impact of formulating rAd35.CS vaccine with aluminium phosphate adjuvant (AlPO(4)) on its immunogenicity.
  • * To assess the preservation of rAd35 viral infectivity and vaccine stability when combined with AlPO(4).

Main Methods:

  • * Formulation of rAd35.CS vaccine with AlPO(4) adjuvant.
  • * Assessment of rAd35 viral infectivity in mammalian cells in vitro.
  • * Immunization of mice with the formulated vaccine using single and prime-boost regimens.
  • * Quantification of CS-specific T and B cell responses.

Main Results:

  • * No adverse absorption of rAd35.CS to AlPO(4) was observed, unlike with conventional protein vaccines.
  • * In vitro infectivity of the rAd35 viral vector was maintained after formulation with AlPO(4).
  • * Significantly higher CS-specific T and B cell responses were achieved in mice immunized with rAd35.CS formulated with AlPO(4) compared to the unadjuvanted vaccine.

Conclusions:

  • * Aluminium phosphate (AlPO(4)) adjuvant can be effectively used to enhance the immunogenicity of live Adenovirus serotype 35-based vaccines.
  • * This formulation strategy offers a feasible method to increase the potency of rAd35.CS malaria vaccines.
  • * The combination preserves viral vector integrity and in vitro infectivity while boosting cellular immune responses.