ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
WHO , 2023. World Malaria Report 2023. Geneva, Switzerland: World Health Organization.
-
2.
Sinnis P , Fidock DA , 2022. The RTS,S vaccine – a chance to regain the upper hand against malaria? Cell 185: 750–754.
-
3.
WHO , 2022. Malaria Vaccine: WHO Position Paper—March 2022. Geneva, Switzerland: World Health Organization.
-
4.
United Nations , 2023. WHO Approves Second Malaria Vaccine for Children. Available at: https://news.un.org/en/story/2023/10/1141787. Accessed October 3, 2023.
-
5.
Conrad MD , Rosenthal PJ , 2019. Antimalarial drug resistance in Africa: The calm before the storm? Lancet Infect Dis 19: e338–e351.
-
6.
Moyes CL , Athinya DK , Seethaler T , Battle KE , Sinka M , Hadi MP , Hemingway J , Coleman M , Hancock PA , 2020. Evaluating insecticide resistance across African districts to aid malaria control decisions. Proc Natl Acad Sci USA 117: 22042–22050.
-
7.
Vogel G , 2023. Second malaria vaccine gets WHO green light. Science 382: 16–17.
-
8.
Baral R et al., 2023. Cost of introducing and delivering RTS,S/AS01 malaria vaccine within the malaria vaccine implementation program. Vaccine 41: 1496–1502.
-
9.
Merle CS , RTSS-SMC Working Group , 2023. Implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission: Workshop meeting report. Malar J 22: 242.
-
10.
RTS,S Clinical Trials Partnership , et al.2011. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med 365: 1863–1875.
-
11.
RTS,S Clinical Trials Partnership , 2015. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomised, controlled trial. Lancet 386: 31–45.
-
12.
RTS,S Clinical Trials Partnership , 2014. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: A phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med 11: e1001685.
-
13.
Kurtovic L , Agius PA , Feng G , Drew DR , Ubillos I , Sacarlal J , Aponte JJ , Fowkes FJI , Dobano C , Beeson JG , 2019. Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure. BMC Med 17: 45.
-
14.
Feng G et al., 2022. Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children. BMC Med 20: 289.
-
15.
White MT et al., 2014. A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med 12: 117.
-
16.
White MT et al., 2015. Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: Secondary analysis of data from a phase 3 randomised controlled trial. Lancet Infect Dis 15: 1450–1458.
-
17.
Ubillos I et al., 2018. Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children. BMC Med 16: 197.
-
18.
Olotu A et al., 2013. Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. N Engl J Med 368: 1111–1120.
-
19.
Wahl I , Wardemann H , 2022. How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein. J Exp Med 219: e20201313.
-
20.
Beeson JG , Kurtovic L , Dobano C , Opi DH , Chan JA , Feng G , Good MF , Reiling L , Boyle MJ , 2019. Challenges and strategies for developing efficacious and long-lasting malaria vaccines. Sci Transl Med 11: eaau1458.
-
21.
Dobano C et al., 2019. Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy. Nat Commun 10: 2174.
-
22.
Suscovich TJ et al., 2020. Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination. Sci Transl Med 12: eabb4757.
-
23.
Kurtovic L et al., 2021. Multifunctional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase 1/2a trial. J Infect Dis 224: 1128–1138.
-
24.
Das J et al., 2021. Delayed fractional dosing with RTS,S/AS01 improves humoral immunity to malaria via a balance of polyfunctional NANP6- and Pf16-specific antibodies. Med (NY) 2: 1269–1286.e9.
-
25.
Seaton KE et al., 2021. Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection. NPJ Vaccines 6: 110.
-
26.
Young WC et al., 2021. Comprehensive data integration approach to assess immune responses and correlates of RTS,S/AS01-mediated protection from malaria infection in controlled human malaria infection trials. Front Big Data 4: 672460.
-
27.
Elliott SR , Fowkes FJ , Richards JS , Reiling L , Drew DR , Beeson JG , 2014. Research priorities for the development and implementation of serological tools for malaria surveillance. F1000Prime Rep 6: 100.
-
28.
Seder RA et al., 2013. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341: 1359–1365.
-
29.
Sissoko MS et al., 2017. Safety and efficacy of PfSPZ vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: A randomised, double-blind phase 1 trial. Lancet Infect Dis 17: 498–509.
-
30.
Oneko M et al., 2021. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: A double-blind, randomized, placebo-controlled phase 2 trial. Nat Med 27: 1636–1645.
-
31.
Ewer KJ et al., 2013. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun 4: 2836.
-
32.
Ogwang C et al., 2015. Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults. Sci Transl Med 7: 286re5.
-
33.
Tiono AB et al., 2018. First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5–17 months old infants and children. PLoS One 13: e0208328.
-
34.
Morter R , Tiono AB , Nebie I , Hague O , Ouedraogo A , Diarra A , Viebig NK , Hill AVS , Ewer KJ , Sirima SB , 2022. Impact of exposure to malaria and nutritional status on responses to the experimental malaria vaccine ChAd63 MVA ME-TRAP in 5–17 month-old children in Burkina Faso. Front Immunol 13: 1058227.
-
35.
Tiono AB , Palacpac NMQ , Bougouma EC , Nebie I , Ouedraogo A , Houard S , Arisue N , D’Alessio F , Horii T , Sirima SB , 2023. Plasmodium falciparum infection coinciding with the malaria vaccine candidate BK-SE36 administration interferes with the immune responses in Burkinabe children. Front Immunol 14: 1119820.
-
36.
Fourati S et al., 2016. Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination. Nat Commun 7: 10369.
-
37.
Bartholomeus E et al., 2018. Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders. Vaccine 36: 6282–6289.
-
38.
Qiu S et al., 2018. Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis. Hum Vaccin Immunother 14: 1763–1772.
-
39.
Querec TD et al., 2009. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10: 116–125.
-
40.
Tsang JS et al., 2014. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell 157: 499–513.
-
41.
HIPC-CHI Signatures Project Team , HIPC-I Consortium , 2017. Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol 2: eaal4656.
-
42.
Moncunill G et al., 2022. Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: A matched case-control study. eLife 11: e70393.
-
43.
Chandramohan D et al., 2021. Seasonal malaria vaccination with or without seasonal malaria chemoprevention. N Engl J Med 385: 1005–1017.
-
44.
Dicko A et al., 2023. Seasonal vaccination with RTS,S/AS01(E) vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: A double-blind, randomised, controlled, phase 3 trial. Lancet Infect Dis 24: 75–86.
-
45.
WHO , 2022. WHO Guidelines for Malaria. Geneva, Switzerland: World Health Organization.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 2870 | 2206 | 319 |
| Full Text Views | 156 | 87 | 12 |
| PDF Downloads | 193 | 102 | 12 |
Previous Malaria Exposures and Immune Dysregulation: Developing Strategies To Improve Malaria Vaccine Efficacy in Young Children
Katherine R. Dobbs
Katherine R. Dobbs
Case Western Reserve University School of Medicine, Cleveland, Ohio;
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Harrysone E. Atieli
Harrysone E. Atieli
Tom Mboya University, Homa Bay, Kenya;
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Clarissa Valim
Clarissa Valim
Boston University School of Public Health, Boston, Massachusetts;
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James G. Beeson
James G. Beeson
Burnet Institute, Melbourne, Victoria, Australia
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ABSTRACT.
After several decades in development, two malaria vaccines based on the same antigen and with very similar constructs and adjuvants, RTS,S/AS01 (RTS,S) and R21/Matrix-M (R21), were recommended by the WHO for widespread vaccination of children. These vaccines are much-needed additions to malaria control programs that, when used in conjunction with other control measures, will help to accelerate reductions in malaria morbidity and mortality. Although R21 is not yet available, RTS,S is currently being integrated into routine vaccine schedules in some areas. However, the efficacy of RTS,S is partial, short-lived, and varies widely according to age and geographic location. It is not clear why RTS,S induces protection in some individuals and not others, what the immune mechanisms are that favor protective immunity with RTS,S, and how immune mechanisms are influenced by host and environmental factors. Several studies suggest that higher levels of previous malaria exposure negatively impact RTS,S clinical efficacy. In this article, we summarize data suggesting that previous malaria exposures negatively impact the efficacy of RTS,S and other malaria vaccine candidates. We highlight recent evidence suggesting that increasing malaria exposure impairs the generation of functional antibody responses to RTS,S. Finally, we discuss how investigation of clinical and immune factors associated with suboptimal responses to RTS,S can be used to develop strategies to optimize RTS,S, which will remain relevant to R21 and next-generation vaccines.
Author Notes
Authors’ addresses: Katherine R. Dobbs, Case Western Reserve University School of Medicine, Cleveland, OH, E-mail: kxd179@case.edu. Harrysone E. Atieli, Tom Mboya University, Homa Bay, Kenya, E-mail: etemesi2012@yahoo.com. Clarissa Valim, Boston University School of Public Health, Boston, MA, E-mail: cvalim@bu.edu. James G. Beeson, Burnet Institute, Melbourne, Victoria, Australia, E-mail: james.beeson@burnet.edu.au.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
WHO , 2023. World Malaria Report 2023. Geneva, Switzerland: World Health Organization.
-
2.
Sinnis P , Fidock DA , 2022. The RTS,S vaccine – a chance to regain the upper hand against malaria? Cell 185: 750–754.
-
3.
WHO , 2022. Malaria Vaccine: WHO Position Paper—March 2022. Geneva, Switzerland: World Health Organization.
-
4.
United Nations , 2023. WHO Approves Second Malaria Vaccine for Children. Available at: https://news.un.org/en/story/2023/10/1141787. Accessed October 3, 2023.
-
5.
Conrad MD , Rosenthal PJ , 2019. Antimalarial drug resistance in Africa: The calm before the storm? Lancet Infect Dis 19: e338–e351.
-
6.
Moyes CL , Athinya DK , Seethaler T , Battle KE , Sinka M , Hadi MP , Hemingway J , Coleman M , Hancock PA , 2020. Evaluating insecticide resistance across African districts to aid malaria control decisions. Proc Natl Acad Sci USA 117: 22042–22050.
-
7.
Vogel G , 2023. Second malaria vaccine gets WHO green light. Science 382: 16–17.
-
8.
Baral R et al., 2023. Cost of introducing and delivering RTS,S/AS01 malaria vaccine within the malaria vaccine implementation program. Vaccine 41: 1496–1502.
-
9.
Merle CS , RTSS-SMC Working Group , 2023. Implementation strategies for the introduction of the RTS,S/AS01 (RTS,S) malaria vaccine in countries with areas of highly seasonal transmission: Workshop meeting report. Malar J 22: 242.
-
10.
RTS,S Clinical Trials Partnership , et al.2011. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children. N Engl J Med 365: 1863–1875.
-
11.
RTS,S Clinical Trials Partnership , 2015. Efficacy and safety of RTS,S/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: Final results of a phase 3, individually randomised, controlled trial. Lancet 386: 31–45.
-
12.
RTS,S Clinical Trials Partnership , 2014. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: A phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med 11: e1001685.
-
13.
Kurtovic L , Agius PA , Feng G , Drew DR , Ubillos I , Sacarlal J , Aponte JJ , Fowkes FJI , Dobano C , Beeson JG , 2019. Induction and decay of functional complement-fixing antibodies by the RTS,S malaria vaccine in children, and a negative impact of malaria exposure. BMC Med 17: 45.
-
14.
Feng G et al., 2022. Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children. BMC Med 20: 289.
-
15.
White MT et al., 2014. A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine. BMC Med 12: 117.
-
16.
White MT et al., 2015. Immunogenicity of the RTS,S/AS01 malaria vaccine and implications for duration of vaccine efficacy: Secondary analysis of data from a phase 3 randomised controlled trial. Lancet Infect Dis 15: 1450–1458.
-
17.
Ubillos I et al., 2018. Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children. BMC Med 16: 197.
-
18.
Olotu A et al., 2013. Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. N Engl J Med 368: 1111–1120.
-
19.
Wahl I , Wardemann H , 2022. How to induce protective humoral immunity against Plasmodium falciparum circumsporozoite protein. J Exp Med 219: e20201313.
-
20.
Beeson JG , Kurtovic L , Dobano C , Opi DH , Chan JA , Feng G , Good MF , Reiling L , Boyle MJ , 2019. Challenges and strategies for developing efficacious and long-lasting malaria vaccines. Sci Transl Med 11: eaau1458.
-
21.
Dobano C et al., 2019. Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy. Nat Commun 10: 2174.
-
22.
Suscovich TJ et al., 2020. Mapping functional humoral correlates of protection against malaria challenge following RTS,S/AS01 vaccination. Sci Transl Med 12: eabb4757.
-
23.
Kurtovic L et al., 2021. Multifunctional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase 1/2a trial. J Infect Dis 224: 1128–1138.
-
24.
Das J et al., 2021. Delayed fractional dosing with RTS,S/AS01 improves humoral immunity to malaria via a balance of polyfunctional NANP6- and Pf16-specific antibodies. Med (NY) 2: 1269–1286.e9.
-
25.
Seaton KE et al., 2021. Subclass and avidity of circumsporozoite protein specific antibodies associate with protection status against malaria infection. NPJ Vaccines 6: 110.
-
26.
Young WC et al., 2021. Comprehensive data integration approach to assess immune responses and correlates of RTS,S/AS01-mediated protection from malaria infection in controlled human malaria infection trials. Front Big Data 4: 672460.
-
27.
Elliott SR , Fowkes FJ , Richards JS , Reiling L , Drew DR , Beeson JG , 2014. Research priorities for the development and implementation of serological tools for malaria surveillance. F1000Prime Rep 6: 100.
-
28.
Seder RA et al., 2013. Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. Science 341: 1359–1365.
-
29.
Sissoko MS et al., 2017. Safety and efficacy of PfSPZ vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: A randomised, double-blind phase 1 trial. Lancet Infect Dis 17: 498–509.
-
30.
Oneko M et al., 2021. Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: A double-blind, randomized, placebo-controlled phase 2 trial. Nat Med 27: 1636–1645.
-
31.
Ewer KJ et al., 2013. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun 4: 2836.
-
32.
Ogwang C et al., 2015. Prime-boost vaccination with chimpanzee adenovirus and modified vaccinia Ankara encoding TRAP provides partial protection against Plasmodium falciparum infection in Kenyan adults. Sci Transl Med 7: 286re5.
-
33.
Tiono AB et al., 2018. First field efficacy trial of the ChAd63 MVA ME-TRAP vectored malaria vaccine candidate in 5–17 months old infants and children. PLoS One 13: e0208328.
-
34.
Morter R , Tiono AB , Nebie I , Hague O , Ouedraogo A , Diarra A , Viebig NK , Hill AVS , Ewer KJ , Sirima SB , 2022. Impact of exposure to malaria and nutritional status on responses to the experimental malaria vaccine ChAd63 MVA ME-TRAP in 5–17 month-old children in Burkina Faso. Front Immunol 13: 1058227.
-
35.
Tiono AB , Palacpac NMQ , Bougouma EC , Nebie I , Ouedraogo A , Houard S , Arisue N , D’Alessio F , Horii T , Sirima SB , 2023. Plasmodium falciparum infection coinciding with the malaria vaccine candidate BK-SE36 administration interferes with the immune responses in Burkinabe children. Front Immunol 14: 1119820.
-
36.
Fourati S et al., 2016. Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination. Nat Commun 7: 10369.
-
37.
Bartholomeus E et al., 2018. Transcriptome profiling in blood before and after hepatitis B vaccination shows significant differences in gene expression between responders and non-responders. Vaccine 36: 6282–6289.
-
38.
Qiu S et al., 2018. Significant transcriptome and cytokine changes in hepatitis B vaccine non-responders revealed by genome-wide comparative analysis. Hum Vaccin Immunother 14: 1763–1772.
-
39.
Querec TD et al., 2009. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans. Nat Immunol 10: 116–125.
-
40.
Tsang JS et al., 2014. Global analyses of human immune variation reveal baseline predictors of postvaccination responses. Cell 157: 499–513.
-
41.
HIPC-CHI Signatures Project Team , HIPC-I Consortium , 2017. Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Sci Immunol 2: eaal4656.
-
42.
Moncunill G et al., 2022. Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: A matched case-control study. eLife 11: e70393.
-
43.
Chandramohan D et al., 2021. Seasonal malaria vaccination with or without seasonal malaria chemoprevention. N Engl J Med 385: 1005–1017.
-
44.
Dicko A et al., 2023. Seasonal vaccination with RTS,S/AS01(E) vaccine with or without seasonal malaria chemoprevention in children up to the age of 5 years in Burkina Faso and Mali: A double-blind, randomised, controlled, phase 3 trial. Lancet Infect Dis 24: 75–86.
-
45.
WHO , 2022. WHO Guidelines for Malaria. Geneva, Switzerland: World Health Organization.
| Past two years | Past Year | Past 30 Days | |
|---|---|---|---|
| Abstract Views | 2870 | 2206 | 319 |
| Full Text Views | 156 | 87 | 12 |
| PDF Downloads | 193 | 102 | 12 |