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ResearchIn-Press PreviewImmunologyInfectious disease Open Access | 10.1172/jci.insight.207272

Pan-African hybridization of PfSPZ increases antigenic diversity and replicative capacity for malaria vaccine design

Lucia Pazzagli,1 Bethany Jenkins,2 Ankit Dwivedi,3 Asha Patil,2 Yonas Abebe,2 Tales V. Pascini,2 Urvashi Rai,2 Priya Gupta,4 Nastaran Rezakhani,4 Chakshu Gandhi,3 Yiwei Yang,3 Sudhir Kumar,4 Mohd Kamil,1 Gigliola Zanghí,4 Manuel Llinás,5 Stephen L. Hoffman,2 Joana C. Silva,3 Ashley M. Vaughan,6 and B. Kim Lee Sim2

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Pazzagli, L. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Jenkins, B. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Dwivedi, A. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Patil, A. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

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1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Pascini, T. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Rai, U. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

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1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Rezakhani, N. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

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1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Yang, Y. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Kumar, S. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Kamil, M. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Zanghí, G. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Llinás, M. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Hoffman, S. in: PubMed | Google Scholar |

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Silva, J. in: PubMed | Google Scholar |

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Vaughan, A. in: PubMed | Google Scholar

1Center for Global Infectious Disease Research, Seattle Children’s Research Institute, Seattle, United States of America

2Sanaria Inc., Rockville, United States of America

3Institute for Genome Sciences, University of Maryland, Baltimore, United States of America

4Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, United States of America

5Department of Biochemistry and Molecular Biology and of Chemistry, Huck Cen, The Pennsylvania State University, University Park, United States of America

6Center for Global Infectious Disease Research, Seattle Childrens Research Institute, Seattle, United States of America

Find articles by Sim, B. in: PubMed | Google Scholar

Published August 18, 2026 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.207272.
Copyright © 2026, Pazzagli et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published August 18, 2026 - Version history
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Abstract

Plasmodium falciparum sporozoite (PfSPZ) vaccines, comprised of aseptic, purified, live parasites that arrest during or just after liver stage development, show excellent safety and efficacy in humans. They can induce complete protection against Pf infection, mediated primarily by cellular immune responses against parasite antigens expressed in hepatocytes. Current PfSPZ vaccines rely on the West African PfNF54 parasite, which uniquely produces high numbers of PfSPZ in mosquitoes, facilitating manufacturing efficiency. However, PfNF54 has relatively low hepatocyte infectivity, limiting potency. We created hybrid pan-African Pf strains by genetically crossing PfNF54 with East African Pf strains. The hybrid, AV27, was selected for development based on balanced contribution of parental genomes, high PfSPZ production and high liver stage infectivity. As compared to NF54-based PfSPZ vaccines, we expect AV27-based vaccines will have greater and broader efficacy at lower doses due to higher liver stage infectivity and inclusion of unique East African CD8+ T cell epitopes.

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