Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

Judith E. Epstein; Kristopher M. Paolino; Thomas L. Richie; Martha Sedegah; Alexandra Singer; Adam J. Ruben; Sumana Chakravarty; April Stafford; Richard C. Ruck; Abraham G. Eappen; Tao Li; Peter F. Billingsley; Anita Manoj; Joana C. Silva; Kara Moser; Robin Nielsen; Donna Tosh; Susan Cicatelli; Harini Ganeshan; Jessica Case; Debbie Padilla; Silas Davidson; Lindsey Garver; Elizabeth Saverino; Tooba Murshedkar; Anusha Gunasekera; Patrick S. Twomey; Sharina Reyes; James E. Moon; Eric R. James; K. C. Natasha; Minglin Li; Esteban Abot; Arnel Belmonte; Kevin Hauns; Maria Belmonte; Jun Huang; Carlos Vasquez; Shon Remich; Mary Carrington; Yonas Abebe; Amy Tillman; Bradley Hickey; Jason Regules; Eileen Villasante; B. Kim Lee Sim; Stephen L. Hoffman

doi:10.1172/jci.insight.89154

Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

Judith E. Epstein, Kristopher M. Paolino, Thomas L. Richie, Martha Sedegah, Alexandra Singer, Adam J. Ruben, Sumana Chakravarty, April Stafford, Richard C. Ruck, Abraham G. Eappen, Tao Li, Peter F. Billingsley, Anita Manoj, Joana C. Silva, Kara Moser, Robin Nielsen, Donna Tosh, Susan Cicatelli, Harini Ganeshan, Jessica CaseDebbie Padilla, Silas Davidson, Lindsey Garver, Elizabeth Saverino, Tooba Murshedkar, Anusha Gunasekera, Patrick S. Twomey, Sharina Reyes, James E. Moon, Eric R. James, K. C. Natasha, Minglin Li, Esteban Abot, Arnel Belmonte, Kevin Hauns, Maria Belmonte, Jun Huang, Carlos Vasquez, Shon Remich, Mary Carrington, Yonas Abebe, Amy Tillman, Bradley Hickey, Jason Regules, Eileen Villasante, B. Kim Lee Sim, Stephen L. Hoffman

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

Abstract

BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 10⁵ PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 10⁵ PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [–35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria.

Original language	English
Article number	:e89154
Journal	JCI Insight
Volume	2
Issue number	1
DOIs	https://doi.org/10.1172/jci.insight.89154
State	Published - 12 Jan 2017
Externally published	Yes

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Epstein, J. E., Paolino, K. M., Richie, T. L., Sedegah, M., Singer, A., Ruben, A. J., Chakravarty, S., Stafford, A., Ruck, R. C., Eappen, A. G., Li, T., Billingsley, P. F., Manoj, A., Silva, J. C., Moser, K., Nielsen, R., Tosh, D., Cicatelli, S., Ganeshan, H., ... Hoffman, S. L. (2017). Protection against Plasmodium falciparum malaria by PfSPZ Vaccine. JCI Insight, 2(1), Article :e89154. https://doi.org/10.1172/jci.insight.89154

@article{af8825971f5644bb9d697564f85e869c,

title = "Protection against Plasmodium falciparum malaria by PfSPZ Vaccine",

abstract = "BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105 PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105 PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [–35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria.",

author = "Epstein, {Judith E.} and Paolino, {Kristopher M.} and Richie, {Thomas L.} and Martha Sedegah and Alexandra Singer and Ruben, {Adam J.} and Sumana Chakravarty and April Stafford and Ruck, {Richard C.} and Eappen, {Abraham G.} and Tao Li and Billingsley, {Peter F.} and Anita Manoj and Silva, {Joana C.} and Kara Moser and Robin Nielsen and Donna Tosh and Susan Cicatelli and Harini Ganeshan and Jessica Case and Debbie Padilla and Silas Davidson and Lindsey Garver and Elizabeth Saverino and Tooba Murshedkar and Anusha Gunasekera and Twomey, {Patrick S.} and Sharina Reyes and Moon, {James E.} and James, {Eric R.} and Natasha, {K. C.} and Minglin Li and Esteban Abot and Arnel Belmonte and Kevin Hauns and Maria Belmonte and Jun Huang and Carlos Vasquez and Shon Remich and Mary Carrington and Yonas Abebe and Amy Tillman and Bradley Hickey and Jason Regules and Eileen Villasante and {Kim Lee Sim}, B. and Hoffman, {Stephen L.}",

year = "2017",

month = jan,

day = "12",

doi = "10.1172/jci.insight.89154",

language = "English",

volume = "2",

journal = "JCI Insight",

issn = "2379-3708",

number = "1",

}

Epstein, JE, Paolino, KM, Richie, TL, Sedegah, M, Singer, A, Ruben, AJ, Chakravarty, S, Stafford, A, Ruck, RC, Eappen, AG, Li, T, Billingsley, PF, Manoj, A, Silva, JC, Moser, K, Nielsen, R, Tosh, D, Cicatelli, S, Ganeshan, H, Case, J, Padilla, D, Davidson, S, Garver, L, Saverino, E, Murshedkar, T, Gunasekera, A, Twomey, PS, Reyes, S, Moon, JE, James, ER, Natasha, KC, Li, M, Abot, E, Belmonte, A, Hauns, K, Belmonte, M, Huang, J, Vasquez, C, Remich, S, Carrington, M, Abebe, Y, Tillman, A, Hickey, B, Regules, J, Villasante, E, Kim Lee Sim, B & Hoffman, SL 2017, 'Protection against Plasmodium falciparum malaria by PfSPZ Vaccine', JCI Insight, vol. 2, no. 1, :e89154. https://doi.org/10.1172/jci.insight.89154

TY - JOUR

T1 - Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

AU - Epstein, Judith E.

AU - Paolino, Kristopher M.

AU - Richie, Thomas L.

AU - Sedegah, Martha

AU - Singer, Alexandra

AU - Ruben, Adam J.

AU - Chakravarty, Sumana

AU - Stafford, April

AU - Ruck, Richard C.

AU - Eappen, Abraham G.

AU - Li, Tao

AU - Billingsley, Peter F.

AU - Manoj, Anita

AU - Silva, Joana C.

AU - Moser, Kara

AU - Nielsen, Robin

AU - Tosh, Donna

AU - Cicatelli, Susan

AU - Ganeshan, Harini

AU - Case, Jessica

AU - Padilla, Debbie

AU - Davidson, Silas

AU - Garver, Lindsey

AU - Saverino, Elizabeth

AU - Murshedkar, Tooba

AU - Gunasekera, Anusha

AU - Twomey, Patrick S.

AU - Reyes, Sharina

AU - Moon, James E.

AU - James, Eric R.

AU - Natasha, K. C.

AU - Li, Minglin

AU - Abot, Esteban

AU - Belmonte, Arnel

AU - Hauns, Kevin

AU - Belmonte, Maria

AU - Huang, Jun

AU - Vasquez, Carlos

AU - Remich, Shon

AU - Carrington, Mary

AU - Abebe, Yonas

AU - Tillman, Amy

AU - Hickey, Bradley

AU - Regules, Jason

AU - Villasante, Eileen

AU - Kim Lee Sim, B.

AU - Hoffman, Stephen L.

PY - 2017/1/12

Y1 - 2017/1/12

N2 - BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105 PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105 PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [–35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria.

AB - BACKGROUND: A radiation-attenuated Plasmodium falciparum (Pf) sporozoite (SPZ) malaria vaccine, PfSPZ Vaccine, protected 6 of 6 subjects (100%) against homologous Pf (same strain as in the vaccine) controlled human malaria infection (CHMI) 3 weeks after 5 doses administered intravenously. The next step was to assess protective efficacy against heterologous Pf (different from Pf in the vaccine), after fewer doses, and at 24 weeks. METHODS: The trial assessed tolerability, safety, immunogenicity, and protective efficacy of direct venous inoculation (DVI) of 3 or 5 doses of PfSPZ Vaccine in non-immune subjects. RESULTS: Three weeks after final immunization, 5 doses of 2.7 × 105 PfSPZ protected 12 of 13 recipients (92.3% [95% CI: 48.0, 99.8]) against homologous CHMI and 4 of 5 (80.0% [10.4, 99.5]) against heterologous CHMI; 3 doses of 4.5 × 105 PfSPZ protected 13 of 15 (86.7% [35.9, 98.3]) against homologous CHMI. Twenty-four weeks after final immunization, the 5-dose regimen protected 7 of 10 (70.0% [17.3, 93.3]) against homologous and 1 of 10 (10.0% [–35.8, 45.6]) against heterologous CHMI; the 3-dose regimen protected 8 of 14 (57.1% [21.5, 76.6]) against homologous CHMI. All 22 controls developed Pf parasitemia. PfSPZ Vaccine was well tolerated, safe, and easy to administer. No antibody or T cell responses correlated with protection. CONCLUSIONS: We have demonstrated for the first time to our knowledge that PfSPZ Vaccine can protect against a 3-week heterologous CHMI in a limited group of malaria-naive adult subjects. A 3-dose regimen protected against both 3-week and 24-week homologous CHMI (87% and 57%, respectively) in this population. These results provide a foundation for developing an optimized immunization regimen for preventing malaria.

UR - http://www.scopus.com/inward/record.url?scp=85014580951&partnerID=8YFLogxK

U2 - 10.1172/jci.insight.89154

DO - 10.1172/jci.insight.89154

M3 - Article

AN - SCOPUS:85014580951

SN - 2379-3708

VL - 2

JO - JCI Insight

JF - JCI Insight

IS - 1

M1 - :e89154

ER -

Protection against Plasmodium falciparum malaria by PfSPZ Vaccine

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