Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection
Abstract Background The World Health Organization (WHO) has called for new malaria vaccines with > 90% efficacy against Plasmodium falciparum infection to expand the anti-disease benefit provided by the RTS,S/AS01 and R21/Matrix M subunit vaccines currently administered to infants and young child...
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BMC
2025-03-01
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| Series: | Malaria Journal |
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| Online Access: | https://doi.org/10.1186/s12936-025-05299-5 |
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| author | Andrea A. Berry Thomas L. Richie L. W. Preston Church Matthew B. Laurens Colleen Boyce Natasha KC Sudhaunshu Joshi Abra Rachida Koudjra Lauryn Butler Mei-Chun Chen Yonas Abebe Tooba Murshedkar Eric R. James Peter F. Billingsley B. Kim Lee Sim Stephen L. Hoffman Kirsten E. Lyke |
| author_facet | Andrea A. Berry Thomas L. Richie L. W. Preston Church Matthew B. Laurens Colleen Boyce Natasha KC Sudhaunshu Joshi Abra Rachida Koudjra Lauryn Butler Mei-Chun Chen Yonas Abebe Tooba Murshedkar Eric R. James Peter F. Billingsley B. Kim Lee Sim Stephen L. Hoffman Kirsten E. Lyke |
| author_sort | Andrea A. Berry |
| collection | DOAJ |
| description | Abstract Background The World Health Organization (WHO) has called for new malaria vaccines with > 90% efficacy against Plasmodium falciparum infection to expand the anti-disease benefit provided by the RTS,S/AS01 and R21/Matrix M subunit vaccines currently administered to infants and young children in sub-Saharan Africa. Attenuated P. falciparum sporozoites (PfSPZ) are being developed as a traveller’s vaccine and to fulfill WHO’s call for high-level efficacy in endemic countries to support malaria elimination. Methods PfSPZ Vaccine, comprised of radiation-attenuated PfSPZ, was compared with normal saline placebo in a randomized, double-blind trial targeting 60 malaria-naive US adults to assess safety, tolerability, immunogenicity, and efficacy against heterologous controlled human malaria infection three and twelve weeks after immunization. Pharmacists provided syringes to blinded clinicians using 3:1 (vaccine:placebo) blocked randomization, for administration by direct venous inoculation on days 1 and 8 (multidose prime) and day 29 (boost), a condensed regimen with superior efficacy. Primary outcomes included adverse events and antibody responses to the P. falciparum circumsporozoite protein (PfCSP). Results 31 participants were screened, randomized and immunized twice (V1, V2) 5–7 days apart, with one withdrawal after an intercurrent adverse event. A vial issue, later traced to the vial manufacturer, halted further immunizations. Solicited local and systemic adverse events recorded for 2 and 7 days after immunizations, respectively, occurred with equal frequency and severity in the 23 vaccinees and 7 controls receiving two immunizations, as did unsolicited adverse events recorded for 28 days and laboratory abnormalities 1 and 5 weeks after V2. Four of 23 vaccinees and one of 7 controls (p = 1.00) developed grade 2 adverse events including subjective fever, headache, malaise, fatigue, rigors, arthralgia and myalgia after V2 but not V1, these symptoms generally resolving within 24 h. Twenty-two of 23 (96%) vaccinees developed IgG (median 99-fold increase over baseline) and IgM (median 1,110-fold increase) antibodies to PfCSP one week after V2. Antibody responses were not associated with reactogenicity. Conclusions The two-dose priming immunization regimen was safe, well tolerated and highly immunogenic. Larger studies may better define the adverse event profile of condensed regimens of PfSPZ Vaccine in malaria-naive adults. Trial registration number: clinicaltrial.gov NCT05604521. |
| format | Article |
| id | doaj-art-ff6e8c1eaa9547d2adc99b01ee6b8ac3 |
| institution | Kabale University |
| issn | 1475-2875 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Malaria Journal |
| spelling | doaj-art-ff6e8c1eaa9547d2adc99b01ee6b8ac32025-08-20T03:41:40ZengBMCMalaria Journal1475-28752025-03-0124111310.1186/s12936-025-05299-5Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infectionAndrea A. Berry0Thomas L. Richie1L. W. Preston Church2Matthew B. Laurens3Colleen Boyce4Natasha KC5Sudhaunshu Joshi6Abra Rachida Koudjra7Lauryn Butler8Mei-Chun Chen9Yonas Abebe10Tooba Murshedkar11Eric R. James12Peter F. Billingsley13B. Kim Lee Sim14Stephen L. Hoffman15Kirsten E. Lyke16Center for Vaccine Development and Global Health, University of Maryland School of MedicineSanaria IncSanaria IncCenter for Vaccine Development and Global Health, University of Maryland School of MedicineCenter for Vaccine Development and Global Health, University of Maryland School of MedicineSanaria IncCenter for Vaccine Development and Global Health, University of Maryland School of MedicineCenter for Vaccine Development and Global Health, University of Maryland School of MedicineCenter for Vaccine Development and Global Health, University of Maryland School of MedicineSanaria IncSanaria IncSanaria IncSanaria IncSanaria IncSanaria IncSanaria IncCenter for Vaccine Development and Global Health, University of Maryland School of MedicineAbstract Background The World Health Organization (WHO) has called for new malaria vaccines with > 90% efficacy against Plasmodium falciparum infection to expand the anti-disease benefit provided by the RTS,S/AS01 and R21/Matrix M subunit vaccines currently administered to infants and young children in sub-Saharan Africa. Attenuated P. falciparum sporozoites (PfSPZ) are being developed as a traveller’s vaccine and to fulfill WHO’s call for high-level efficacy in endemic countries to support malaria elimination. Methods PfSPZ Vaccine, comprised of radiation-attenuated PfSPZ, was compared with normal saline placebo in a randomized, double-blind trial targeting 60 malaria-naive US adults to assess safety, tolerability, immunogenicity, and efficacy against heterologous controlled human malaria infection three and twelve weeks after immunization. Pharmacists provided syringes to blinded clinicians using 3:1 (vaccine:placebo) blocked randomization, for administration by direct venous inoculation on days 1 and 8 (multidose prime) and day 29 (boost), a condensed regimen with superior efficacy. Primary outcomes included adverse events and antibody responses to the P. falciparum circumsporozoite protein (PfCSP). Results 31 participants were screened, randomized and immunized twice (V1, V2) 5–7 days apart, with one withdrawal after an intercurrent adverse event. A vial issue, later traced to the vial manufacturer, halted further immunizations. Solicited local and systemic adverse events recorded for 2 and 7 days after immunizations, respectively, occurred with equal frequency and severity in the 23 vaccinees and 7 controls receiving two immunizations, as did unsolicited adverse events recorded for 28 days and laboratory abnormalities 1 and 5 weeks after V2. Four of 23 vaccinees and one of 7 controls (p = 1.00) developed grade 2 adverse events including subjective fever, headache, malaise, fatigue, rigors, arthralgia and myalgia after V2 but not V1, these symptoms generally resolving within 24 h. Twenty-two of 23 (96%) vaccinees developed IgG (median 99-fold increase over baseline) and IgM (median 1,110-fold increase) antibodies to PfCSP one week after V2. Antibody responses were not associated with reactogenicity. Conclusions The two-dose priming immunization regimen was safe, well tolerated and highly immunogenic. Larger studies may better define the adverse event profile of condensed regimens of PfSPZ Vaccine in malaria-naive adults. Trial registration number: clinicaltrial.gov NCT05604521.https://doi.org/10.1186/s12936-025-05299-5PfSPZVaccinesPlasmodium falciparumMalariaSafetyImmunogenicity |
| spellingShingle | Andrea A. Berry Thomas L. Richie L. W. Preston Church Matthew B. Laurens Colleen Boyce Natasha KC Sudhaunshu Joshi Abra Rachida Koudjra Lauryn Butler Mei-Chun Chen Yonas Abebe Tooba Murshedkar Eric R. James Peter F. Billingsley B. Kim Lee Sim Stephen L. Hoffman Kirsten E. Lyke Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection Malaria Journal PfSPZ Vaccines Plasmodium falciparum Malaria Safety Immunogenicity |
| title | Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection |
| title_full | Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection |
| title_fullStr | Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection |
| title_full_unstemmed | Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection |
| title_short | Safety, tolerability and immunogenicity of a condensed, multi-dose prime regimen of PfSPZ Vaccine for the prevention of Plasmodium falciparum malaria infection |
| title_sort | safety tolerability and immunogenicity of a condensed multi dose prime regimen of pfspz vaccine for the prevention of plasmodium falciparum malaria infection |
| topic | PfSPZ Vaccines Plasmodium falciparum Malaria Safety Immunogenicity |
| url | https://doi.org/10.1186/s12936-025-05299-5 |
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