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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
Abstract:
Previously, we have shown the potency of recombinant Adenovirus serotype 35 viral vaccines (rAd35) to induce strong immune response against the circumsporozoite protein (CS) of the plasmodium parasite. To further optimize immunogenicity of Ad35-based malaria vaccines we formulated rAd35.CS vaccine with aluminium phosphate adjuvant (AlPO(4)). In contrast to the conventional protein based vaccines no absorption to aluminium adjuvant was observed and rAd35 viral in vitro infectivity in mammalian cells was preserved. Immunization with Ad35.CS formulated with AlPO(4) resulted in significantly higher CS specific T and B cell responses in mice upon either single or prime-boost vaccination regimens as compared to rAd35.CS alone. With these results we report for the first time the feasibility of using an AlPO(4) adjuvant to increase the potency of a live adenovirus serotype 35-based vaccine.
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.
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