Scientists have made important strides in understanding how the WHO-endorsed RTS,S malaria vaccine protects children, potentially leading to more effective vaccines against this deadly disease. A recent study examining antibody responses in vaccinated infants found that specific antibodies targeting the malaria parasite’s circumsporozoite protein (CSP) are crucial for protection. Notably, researchers identified the role of IgA antibodies in safeguarding vaccinated children, revealing a previously unknown defense mechanism.
The study also highlighted interesting gender differences in vaccine responses. Men exhibited a stronger protective correlation with certain antibody functions, while women showed a significant protective correlation with certain antibody functions, while women showed significant protection primarily through IgA responses. This finding underscores the need to consider sex-based differences in vaccine development.
Conducted by Dr. Rajesh Kanna Gopal, Dr. Pitchaipillai Sankar Ganesh, and Mr. Naji Naseef Pathoor from Saveetha University in India, this comprehensive review was published in Lancet Microbe. The researchers believe these insights could transform malaria prevention strategies by enhancing specific antibody responses.
While further research in various malaria-endemic regions is necessary, these findings represent a significant advancement in the global effort to combat malaria, particularly in protecting vulnerable children in affected areas. The study was carried out at the Department of Microbiology, Centre for Infectious Diseases, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Science (SIMATS), Chennai, India.
The RTS,S vaccine targets a portion of the circumsporosite protein (CSP) of Plasmodium falciparum, which is the main surface antigen found on sporozoites. These sporozoites are introduced into the body by feeding mosquitoes and migrate through the skin and bloodstream to the liver, where they can cause infection. The vaccine’s goal is to attack sporozoites and prevent infection. Sporozoites may be vulnerable to recognition by antibodies and fc-dependent functions in the skin after being introduced in the blood before they reach the liver.
The research published in The Lancet showed the immune response in young African Children revealed that stronger IgA responses to two specific regions of the CSP protein, the NANP-repeat, and C-terminal regions-were linked to increased protection from the vaccine.
How does IgA respond, how do they protect against malaria?
IgA is the second most abundant immunoglobulin isotype in serum, following IgG, yet it is frequently overlooked in studies focused on malaria vaccines. There was a significant increase in IgA levels targeting the NANP-repeat and C-terminal regions of CSP. Notably, higher magnitudes of IgA significantly reduced malaria risk, which was not reported previously in children.
These findings could generally impact future malaria vaccine strategies. The study suggests that investigating how well antibodies work might provide better insights into protection than measuring the levels of antibodies produced and improve vaccine effectiveness. The protective role of IgA antibodies opens new possibilities for vaccine design.
Reference:
1. Gopal RK, Ganesh PS, Pathoor NN. Functional antibody responses associated with effectiveness of RTS, S malaria vaccine in children: new insights and implications. The Lancet Microbe. 2024 Sep 24.
(Input from various sources)
(Rehash/Josna Lewis/MSM)