User login
New research has revealed markers associated with efficacy of the RTS,S/AS01E malaria vaccine (Mosquirix™).
The study suggests malaria protection depends on the amount and subclass of antibodies generated upon vaccination and on previous exposure levels to the malaria parasite.
Researchers believe these findings, published in BMC Medicine, could aid the development of more effective vaccines and guide efforts to improve the effectiveness of RTS,S.
The RTS,S vaccine demonstrated partial effectiveness in a phase 3 study—31% in infants ages 6 weeks to 12 weeks and 56% in children ages 5 months to 17 months.
Carlota Dobaño Lázaro, PhD, of ISGlobal in Barcelona, Spain, and her colleagues have been working to understand the reasons for this variability and identify vaccine protection correlates.
The team used a quantitative assay to investigate the levels and types of antibodies induced by RTS,S. In particular, they measured total IgM, IgG, and IgG1–4 subclass antibodies to hepatitis B surface antigen (HBsAg) and three constructs of the Plasmodium falciparum circumsporozoite protein (CSP).
The researchers analyzed serum and plasma from 195 infants and children from Kintampo, Ghana (an area with high malaria transmission) and Manhiça, Mozambique (low malaria transmission), who were vaccinated during the phase 3 trial for RTS,S.
The results confirmed that RTS,S induces significant levels of IgG antibodies against both CSP and HBsAg, which are higher in children than in infants.
The researchers found that higher HBsAg antibody levels post-vaccination were associated with protection from malaria.
However, the same could not be said for all subclasses of CSP antibodies. Higher levels of IgG1 and IgG3 antibodies were associated with protection, while higher levels of IgG2 and IgG4 were associated with a greater risk of developing malaria.
“The balance between the different subclasses seems to be more important than the total IgG levels,” said study author Itzi Ubillos Escriche, of ISGlobal.
“This could be because IgG1 and IgG3 antibodies have the capacity to stick to the parasite and give an ‘eat-me’ signal to cells of the immune system.”
The results also showed that subjects with higher pre-vaccine levels of anti-P falciparum and anti-CSP antibodies were less protected against malaria post-vaccination.
“This means that the vaccine will exert a larger benefit to infants who have not been exposed to the parasite in utero or during the first weeks of life,” Dr. Dobaño Lázaro said.
“This study . . . identifies new correlates of vaccine success and failure in African children and provides a basis for designing more efficacious vaccines.”
This research was funded by the National Institutes of Health-National Institute of Allergy and Infectious Diseases, PATH Malaria Vaccine Initiative, Ministerio de Economía y Competitividad, and EVIMalaR and AGAUR-Catalonia. ISGlobal is a member of the CERCA Program, Generalitat de Catalunya.
The authors said they have no competing interests.
The phase 3 trial of RTS,S was supported by GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative.
New research has revealed markers associated with efficacy of the RTS,S/AS01E malaria vaccine (Mosquirix™).
The study suggests malaria protection depends on the amount and subclass of antibodies generated upon vaccination and on previous exposure levels to the malaria parasite.
Researchers believe these findings, published in BMC Medicine, could aid the development of more effective vaccines and guide efforts to improve the effectiveness of RTS,S.
The RTS,S vaccine demonstrated partial effectiveness in a phase 3 study—31% in infants ages 6 weeks to 12 weeks and 56% in children ages 5 months to 17 months.
Carlota Dobaño Lázaro, PhD, of ISGlobal in Barcelona, Spain, and her colleagues have been working to understand the reasons for this variability and identify vaccine protection correlates.
The team used a quantitative assay to investigate the levels and types of antibodies induced by RTS,S. In particular, they measured total IgM, IgG, and IgG1–4 subclass antibodies to hepatitis B surface antigen (HBsAg) and three constructs of the Plasmodium falciparum circumsporozoite protein (CSP).
The researchers analyzed serum and plasma from 195 infants and children from Kintampo, Ghana (an area with high malaria transmission) and Manhiça, Mozambique (low malaria transmission), who were vaccinated during the phase 3 trial for RTS,S.
The results confirmed that RTS,S induces significant levels of IgG antibodies against both CSP and HBsAg, which are higher in children than in infants.
The researchers found that higher HBsAg antibody levels post-vaccination were associated with protection from malaria.
However, the same could not be said for all subclasses of CSP antibodies. Higher levels of IgG1 and IgG3 antibodies were associated with protection, while higher levels of IgG2 and IgG4 were associated with a greater risk of developing malaria.
“The balance between the different subclasses seems to be more important than the total IgG levels,” said study author Itzi Ubillos Escriche, of ISGlobal.
“This could be because IgG1 and IgG3 antibodies have the capacity to stick to the parasite and give an ‘eat-me’ signal to cells of the immune system.”
The results also showed that subjects with higher pre-vaccine levels of anti-P falciparum and anti-CSP antibodies were less protected against malaria post-vaccination.
“This means that the vaccine will exert a larger benefit to infants who have not been exposed to the parasite in utero or during the first weeks of life,” Dr. Dobaño Lázaro said.
“This study . . . identifies new correlates of vaccine success and failure in African children and provides a basis for designing more efficacious vaccines.”
This research was funded by the National Institutes of Health-National Institute of Allergy and Infectious Diseases, PATH Malaria Vaccine Initiative, Ministerio de Economía y Competitividad, and EVIMalaR and AGAUR-Catalonia. ISGlobal is a member of the CERCA Program, Generalitat de Catalunya.
The authors said they have no competing interests.
The phase 3 trial of RTS,S was supported by GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative.
New research has revealed markers associated with efficacy of the RTS,S/AS01E malaria vaccine (Mosquirix™).
The study suggests malaria protection depends on the amount and subclass of antibodies generated upon vaccination and on previous exposure levels to the malaria parasite.
Researchers believe these findings, published in BMC Medicine, could aid the development of more effective vaccines and guide efforts to improve the effectiveness of RTS,S.
The RTS,S vaccine demonstrated partial effectiveness in a phase 3 study—31% in infants ages 6 weeks to 12 weeks and 56% in children ages 5 months to 17 months.
Carlota Dobaño Lázaro, PhD, of ISGlobal in Barcelona, Spain, and her colleagues have been working to understand the reasons for this variability and identify vaccine protection correlates.
The team used a quantitative assay to investigate the levels and types of antibodies induced by RTS,S. In particular, they measured total IgM, IgG, and IgG1–4 subclass antibodies to hepatitis B surface antigen (HBsAg) and three constructs of the Plasmodium falciparum circumsporozoite protein (CSP).
The researchers analyzed serum and plasma from 195 infants and children from Kintampo, Ghana (an area with high malaria transmission) and Manhiça, Mozambique (low malaria transmission), who were vaccinated during the phase 3 trial for RTS,S.
The results confirmed that RTS,S induces significant levels of IgG antibodies against both CSP and HBsAg, which are higher in children than in infants.
The researchers found that higher HBsAg antibody levels post-vaccination were associated with protection from malaria.
However, the same could not be said for all subclasses of CSP antibodies. Higher levels of IgG1 and IgG3 antibodies were associated with protection, while higher levels of IgG2 and IgG4 were associated with a greater risk of developing malaria.
“The balance between the different subclasses seems to be more important than the total IgG levels,” said study author Itzi Ubillos Escriche, of ISGlobal.
“This could be because IgG1 and IgG3 antibodies have the capacity to stick to the parasite and give an ‘eat-me’ signal to cells of the immune system.”
The results also showed that subjects with higher pre-vaccine levels of anti-P falciparum and anti-CSP antibodies were less protected against malaria post-vaccination.
“This means that the vaccine will exert a larger benefit to infants who have not been exposed to the parasite in utero or during the first weeks of life,” Dr. Dobaño Lázaro said.
“This study . . . identifies new correlates of vaccine success and failure in African children and provides a basis for designing more efficacious vaccines.”
This research was funded by the National Institutes of Health-National Institute of Allergy and Infectious Diseases, PATH Malaria Vaccine Initiative, Ministerio de Economía y Competitividad, and EVIMalaR and AGAUR-Catalonia. ISGlobal is a member of the CERCA Program, Generalitat de Catalunya.
The authors said they have no competing interests.
The phase 3 trial of RTS,S was supported by GlaxoSmithKline Biologicals SA and the PATH Malaria Vaccine Initiative.