TY - JOUR
T1 - Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and may enhance protection of anti-CSP monoclonal antibodies
AU - Wilder, Brandon K.
AU - Vigdorovich, Vladimir
AU - Carbonetti, Sara
AU - Minkah, Nana
AU - Hertoghs, Nina
AU - Raappana, Andrew
AU - Cardamone, Hayley
AU - Oliver, Brian G.
AU - Trakhimets, Olesya
AU - Kumar, Sudhir
AU - Dambrauskas, Nicholas
AU - Arredondo, Silvia A.
AU - Camargo, Nelly
AU - Seilie, Annette M.
AU - Murphy, Sean C.
AU - Kappe, Stefan H.I.
AU - Sather, D. Noah
N1 - Funding Information:
We would like to thank the vivarium staff at Seattle Children’s Research Institute for their support of animal studies, and Weldon DeBusk for his assistance with the flow cytometry experiments. Additionally, we would like to thank Dr. Paul T. Edlefsen of the Fred Hutch Cancer Research Center for the helpful discussions of statistical analysis and Drs. Neville K. Kisalu and Robert A. Seder of the NIH VRC for their provision of mAb CIS43. This study was funded by NIH R01 AI117234 to S.H.I.K. and D.N.S.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection (i.e., sterile protection). While such disease reduction is important, these and other results indicate that strategies focusing on CSP alone may not achieve the high levels of sterile protection needed for malaria eradication. Here, we show that monoclonal antibodies (mAbs) recognizing another sporozoite protein, TRAP/SSP2, exhibit a range of inhibitory activity and that these mAbs may augment CSP-based protection despite conferring no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.
AB - Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection (i.e., sterile protection). While such disease reduction is important, these and other results indicate that strategies focusing on CSP alone may not achieve the high levels of sterile protection needed for malaria eradication. Here, we show that monoclonal antibodies (mAbs) recognizing another sporozoite protein, TRAP/SSP2, exhibit a range of inhibitory activity and that these mAbs may augment CSP-based protection despite conferring no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.
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U2 - 10.1038/s41541-022-00480-2
DO - 10.1038/s41541-022-00480-2
M3 - Article
AN - SCOPUS:85130808686
VL - 7
JO - npj Vaccines
JF - npj Vaccines
SN - 2059-0105
IS - 1
M1 - 58
ER -