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Principal Investigator: Patrick Duffy
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $2,649,684
Funding agency: National Institute of Allergy and Infectious Diseases
From our publications this year, we report the following advances in FY2024:
1. Duffy PE, Gorres JP, Healy SA, Fried M. Malaria Vaccines: A New Era. 2024. Nature Reviews Microbiology. Jul 18. doi: 10.1038/s41579-024-01065-7.
In this major review article, we provided an overview of the malaria problem and the Plasmodium parasite, then described the RTS,S and R21 vaccines (the first vaccines for any human parasitic disease), summarizing their benefits and limitations. To inform future development, this Review surveyed the malaria vaccine landscape, highlighting successes and failures over recent decades. A section of the review was dedicated to “Improving upon vaccine immunogens” and in particular, “Pfs230D1 platform optimization”, describing the various carrier proteins and adjuvants that have been tested to maximize Pfs230D1 vaccine activity and efficacy.
2. Scaria PV, Roth N, Schwendt K, Muratova OV, Alani N, Lambert LE, Barnafo EK, Rowe CG, Zaidi IU, Rausch KM, Narum DL, Petsch B, Duffy PE. mRNA vaccines expressing malaria transmission blocking antigens Pfs25 and PFs230D1 induce functional immune response. 2024. npjVaccines. Jan 6; 9(1):9. doi: 10.1038/s41541-023-00783-y.
The recent success of mRNA vaccines revealed the potential of this technology for infectious diseases, and thus we explored the mRNA platform for TBV development. mRNA constructs of Pfs25 and Pfs230D1 variously incorporating signal peptides (SP), GPI anchor, and Trans Membrane (TM) domain were assessed in vitro for antigen expression, and selected constructs were evaluated in mice. Only mRNA constructs with GPI anchor or TM domain yielded strong immune responses in mice. These mRNA constructs generated higher transmission-reducing functional activity versus the corresponding alum-adjuvanted protein-protein conjugates used as comparators. Pfs25 mRNA with GPI anchor or TM maintained >99% transmission reducing activity through the study duration (126 days), demonstrating the potential of mRNA platform for TBV.
Terms: <Adjuvant><Al element><Alum Adjuvant><Aluminum><Antigens><Area><CRM-197><CRM197><Carrier Proteins><Collaborations><Communicable Diseases><Dedications><Development><Effectiveness><Evaluation><Failure><Formulation><Future><Glycans><Goals><Human><Immune response><Immunological response><In Vitro><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Interruption><Liposomal><Liposomes><Malaria><Malaria Vaccines><Malarial Vaccines><Membrane><Membrane Protein Gene><Membrane Proteins><Membrane-Associated Proteins><Meningococcus><Messenger RNA><Mice><Mice Mammals><Microbiology><Modern Man><Murine><Mus><N meningitidis><N. meningitidis><Nature><Needles><Neisseria meningitidis><P vivax><P. vivax><Paludism><Parasites><Parasitic Diseases><Peptide Signal Sequences><Plasmodium><Plasmodium Infections><Plasmodium vivax><Polysaccharides><Proteins><Publications><RNA vaccine><RNA-based vaccine><Recombinant Proteins><Reporting><S enterica serovar Typhi><S typhi><S typhosa><S. enterica serovar Typhi><S. typhi><S. typhosa><Salmonella enterica serovar Typhi><Salmonella typhi><Salmonella typhosa><Scientific Publication><Sexual Development><Signal Peptide><Signal Sequences><Surface><Surface Proteins><Survey Instrument><Surveys><System><TM Domain><Technology><Testing><Tetanus Toxoid><Transmembrane Domain><Transmembrane Region><Transmission><Transport Protein Gene><Transport Proteins><Transporter Protein><Vaccines><alum><aluminum sulfate><burden of disease><burden of illness><controlled release><cross reacting material 197><deliver vaccines><develop a vaccine><develop vaccines><development of a vaccine><developmental><disease burden><host response><immune system response><immunogen><immunoresponse><improved><mRNA><mRNA vaccine><mRNA-based vaccine><malaria transmission><malaria transmission-blocking vaccine><membrane structure><new vaccines><next generation vaccines><novel><novel vaccines><protein complex><protein signal sequence><sex development><success><transmission blocking><transmission process><transmission-blocking vaccine><vaccine delivery><vaccine development><vaccine platform><vaccines against malaria>