TY - JOUR AU - Macià, Dídac AU - Campo, Joseph J. AU - Moncunill, Gemma AU - Jairoce, Chenjerai AU - Nhabomba, Augusto J. AU - Mpina, Maximilian AU - Sorgho, Hermann AU - Dosoo, David AU - Traore, Ousmane AU - Kusi, Kwadwo Asamoah AU - Williams, Nana Aba AU - Oberai, Amit AU - Randall, Arlo AU - Sanz, Hèctor AU - Valim, Clarissa AU - Asante, Kwaku Poku AU - Owusu-Agyei, Seth AU - Tinto, Halidou AU - Agnandji, Selidji Todagbe AU - Kariuki, Simon AU - Gyan, Ben AU - Daubenberger, Claudia AU - Mordmüller, Benjamin AU - Petrone, Paula AU - Dobaño, Carlota T1 - Strong off-target antibody reactivity to malarial antigens induced by RTS,S/AS01E vaccination is associated with protection PY - 2022/05/23/ AB - The RTS,S/AS01E vaccine targets the circumsporozoite protein (CSP) of the Plasmodium falciparum (P. falciparum) parasite. Protein microarrays were used to measure levels of IgG against 1000 P. falciparum antigens in 2138 infants (age 6–12 weeks) and children (age 5–17 months) from 6 African sites of the phase III trial, sampled before and at 4 longitudinal visits after vaccination. One month postvaccination, IgG responses to 17% of all probed antigens showed differences between RTS,S/AS01E and comparator vaccination groups, whereas no prevaccination differences were found. A small subset of antigens presented IgG levels reaching 4- to 8-fold increases in the RTS,S/AS01E group, comparable in magnitude to anti-CSP IgG levels (~11-fold increase). They were strongly cross-correlated and correlated with anti-CSP levels, waning similarly over time and reincreasing with the booster dose. Such an intriguing phenomenon may be due to cross-reactivity of anti-CSP antibodies with these antigens. RTS,S/AS01E vaccinees with strong off-target IgG responses had an estimated lower clinical malaria incidence after adjusting for age group, site, and postvaccination anti-CSP levels. RTS,S/AS01E-induced IgG may bind strongly not only to CSP, but also to unrelated malaria antigens, and this seems to either confer, or at least be a marker of, increased protection from clinical malaria. JF - JCI Insight JA - JCI Insight SN - 2379-3708 DO - 10.1172/jci.insight.158030 VL - 7 IS - 10 UR - https://doi.org/10.1172/jci.insight.158030 PB - The American Society for Clinical Investigation ER -