Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles
Abstract Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-04-01
|
| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-023-00655-5 |
| _version_ | 1827613104291184640 |
|---|---|
| author | Nicholas J. MacDonald Kavita Singh Karine Reiter Vu Nguyen Richard Shimp Apostolos G. Gittis Beth Chen Martin Burkhardt Baoshan Zhang Zhixiong Wang Raul Herrera Mackenzie Moler Duck-Yeon Lee Sachy Orr-Gonzalez Jessica Herrod Lynn E. Lambert Kelly M. Rausch Olga Muratova David S. Jones Yimin Wu Albert J. Jin David N. Garboczi Patrick E. Duffy David L. Narum |
| author_facet | Nicholas J. MacDonald Kavita Singh Karine Reiter Vu Nguyen Richard Shimp Apostolos G. Gittis Beth Chen Martin Burkhardt Baoshan Zhang Zhixiong Wang Raul Herrera Mackenzie Moler Duck-Yeon Lee Sachy Orr-Gonzalez Jessica Herrod Lynn E. Lambert Kelly M. Rausch Olga Muratova David S. Jones Yimin Wu Albert J. Jin David N. Garboczi Patrick E. Duffy David L. Narum |
| author_sort | Nicholas J. MacDonald |
| collection | DOAJ |
| description | Abstract Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA). The recombinant form of Pfs25 first used in humans was identified as Pfs25H, which contained a total of 14 heterologous amino acid residues located at the amino- and carboxyl-termini including a His6 affinity tag. A second recombinant Pfs25, identified as Pfs25M, was produced to remove the heterologous amino acid residues and conjugated to EPA (Pfs25M-EPA). Here, monomeric Pfs25M was characterized biochemically and biophysically for identity, purity, and integrity including protein structure to assess its comparability with Pfs25H. Although the biological activities of Pfs25H and Pfs25M, whether generated by monomeric forms or conjugated nanoparticles, appeared similar, fine-mapping studies with two transmission-blocking monoclonal antibodies detected structural and immunological differences. In addition, evaluation of antisera generated against conjugated Pfs25H or Pfs25M nanoparticles in nonhuman primates identified polyclonal IgG that recognized these structural differences. |
| first_indexed | 2024-03-09T08:33:57Z |
| format | Article |
| id | doaj.art-744dd43cb85546b1a8f8ee76086ef8c5 |
| institution | Directory Open Access Journal |
| issn | 2059-0105 |
| language | English |
| last_indexed | 2024-03-09T08:33:57Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj.art-744dd43cb85546b1a8f8ee76086ef8c52023-12-02T18:54:40ZengNature Portfolionpj Vaccines2059-01052023-04-01811910.1038/s41541-023-00655-5Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticlesNicholas J. MacDonald0Kavita Singh1Karine Reiter2Vu Nguyen3Richard Shimp4Apostolos G. Gittis5Beth Chen6Martin Burkhardt7Baoshan Zhang8Zhixiong Wang9Raul Herrera10Mackenzie Moler11Duck-Yeon Lee12Sachy Orr-Gonzalez13Jessica Herrod14Lynn E. Lambert15Kelly M. Rausch16Olga Muratova17David S. Jones18Yimin Wu19Albert J. Jin20David N. Garboczi21Patrick E. Duffy22David L. Narum23Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthStructural Biology Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthStructural Biology Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthNational Heart, Lung, and Blood InstituteLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Cellular Imaging and Macromolecular Biophysics, National Institute of Biomedical Imaging and Bioengineering, National Institutes of HealthStructural Biology Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthLaboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of HealthAbstract Development of a malaria vaccine that blocks transmission of different parasite stages to humans and mosquitoes is considered critical for elimination efforts. A vaccine using Pfs25, a protein on the surface of zygotes and ookinetes, is under investigation as a transmission-blocking vaccine (TBV) that would interrupt parasite passage from mosquitoes to humans. The most extensively studied Pfs25 TBVs use Pichia pastoris-produced recombinant forms of Pfs25, chemically conjugated to a recombinant carrier protein, ExoProtein A (EPA). The recombinant form of Pfs25 first used in humans was identified as Pfs25H, which contained a total of 14 heterologous amino acid residues located at the amino- and carboxyl-termini including a His6 affinity tag. A second recombinant Pfs25, identified as Pfs25M, was produced to remove the heterologous amino acid residues and conjugated to EPA (Pfs25M-EPA). Here, monomeric Pfs25M was characterized biochemically and biophysically for identity, purity, and integrity including protein structure to assess its comparability with Pfs25H. Although the biological activities of Pfs25H and Pfs25M, whether generated by monomeric forms or conjugated nanoparticles, appeared similar, fine-mapping studies with two transmission-blocking monoclonal antibodies detected structural and immunological differences. In addition, evaluation of antisera generated against conjugated Pfs25H or Pfs25M nanoparticles in nonhuman primates identified polyclonal IgG that recognized these structural differences.https://doi.org/10.1038/s41541-023-00655-5 |
| spellingShingle | Nicholas J. MacDonald Kavita Singh Karine Reiter Vu Nguyen Richard Shimp Apostolos G. Gittis Beth Chen Martin Burkhardt Baoshan Zhang Zhixiong Wang Raul Herrera Mackenzie Moler Duck-Yeon Lee Sachy Orr-Gonzalez Jessica Herrod Lynn E. Lambert Kelly M. Rausch Olga Muratova David S. Jones Yimin Wu Albert J. Jin David N. Garboczi Patrick E. Duffy David L. Narum Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles npj Vaccines |
| title | Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles |
| title_full | Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles |
| title_fullStr | Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles |
| title_full_unstemmed | Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles |
| title_short | Structural and immunological differences in Plasmodium falciparum sexual stage transmission-blocking vaccines comprised of Pfs25-EPA nanoparticles |
| title_sort | structural and immunological differences in plasmodium falciparum sexual stage transmission blocking vaccines comprised of pfs25 epa nanoparticles |
| url | https://doi.org/10.1038/s41541-023-00655-5 |
| work_keys_str_mv | AT nicholasjmacdonald structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT kavitasingh structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT karinereiter structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT vunguyen structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT richardshimp structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT apostolosggittis structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT bethchen structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT martinburkhardt structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT baoshanzhang structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT zhixiongwang structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT raulherrera structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT mackenziemoler structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT duckyeonlee structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT sachyorrgonzalez structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT jessicaherrod structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT lynnelambert structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT kellymrausch structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT olgamuratova structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT davidsjones structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT yiminwu structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT albertjjin structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT davidngarboczi structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT patrickeduffy structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles AT davidlnarum structuralandimmunologicaldifferencesinplasmodiumfalciparumsexualstagetransmissionblockingvaccinescomprisedofpfs25epananoparticles |