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Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.
The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.
RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.
The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.
With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.
The team looked at 2 groups of subjects:
- Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
- Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).
Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.
Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.
In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.
In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.
In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.
In both groups, natural killer (NK) cell signatures were negatively correlated with protection.
“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.
“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”
Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.
“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted. 
Photo by Caitlin Kleiboer
Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.
The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.
RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.
The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.
With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.
The team looked at 2 groups of subjects:
- Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
- Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).
Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.
Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.
In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.
In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.
In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.
In both groups, natural killer (NK) cell signatures were negatively correlated with protection.
“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.
“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”
Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.
“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.
Photo by Caitlin Kleiboer
Researchers say they have identified molecular signatures that could potentially be used to predict whether the malaria vaccine RTS,S will be effective.
The group says the research, published in PNAS, could inform decisions on how RTS,S or other malaria vaccines are deployed or modified.
RTS,S (also known as RTS,S/AS01 or Mosquirix) has been shown to provide partial protection against malaria in phase 2 and phase 3 trials.
The vaccine is scheduled for roll-out through pilot projects in 3 African countries next year, according to the World Health Organization.
With the current study, researchers used a systems biology approach to identify molecular signatures induced after subjects were vaccinated with RTS,S.
The team looked at 2 groups of subjects:
- Individuals vaccinated with the standard RTS,S vaccination regimen, which consists of 3 RTS,S immunizations (RRR)
- Individuals vaccinated first with recombinant adenovirus 35 (Ad35) expressing the circumsporozoite malaria antigen, followed by 2 immunizations with RTS,S (ARR).
Vaccinated subjects were exposed to mosquitoes infected with Plasmodium falciparum 3 weeks after their final immunization.
Both vaccination regimens resulted in about 50% protection from malaria infection. And the researchers identified markers in each group that were associated with protection.
In the RRR group, circumsporozoite protein-specific antibody titers, prior to the challenge with infected mosquitoes, were associated with protection from malaria infection.
In addition, molecular signatures of B and plasma cells detected in peripheral blood mononuclear cells were associated with pre-challenge antibody titers and protection from malaria infection in the RRR group.
In the ARR group, protection from infection was associated with polyfunctional CD4+ T-cell responses 2 weeks after priming with Ad35, early signatures of innate immunity, and dendritic cell activation.
In both groups, natural killer (NK) cell signatures were negatively correlated with protection.
“Many of the genes contained in the predictive signatures are known to be expressed in natural killer cells, which mediate critical immune functions against viruses,” said study author Bali Pulendran, PhD, of Emory University School of Medicine in Atlanta, Georgia.
“It was a surprise to see such a robust ‘NK cell signature’ in predicting success of vaccination against the malaria parasite and raises the hypothesis that such cells may be playing a vital role in orchestrating immunity against malaria.”
Dr Pulendran and his colleagues said the results of this research suggest protective immunity against P falciparum can be achieved via multiple mechanisms.
“The extent to which these candidate signatures of protection can successfully predict vaccine efficacy in other field trials remain to be determined,” Dr Pulendran noted.