Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS, S/AS01<sub>E</sub> Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen <i>A Phase II</i>, <i>Single</i>-<i>Center</i>, <i>Open</i>, <i>Controlled Trial in Infants in Malawi</i>


Witte, Desiree, Cunliffe, Nigel A ORCID: 0000-0002-5449-4988, Turner, Ann M, Ngulube, Edward, Ofori-Anyinam, Opokua, Vekemans, Johan, Chimpeni, Philips, Lievens, Marc, Wilson, Trevor P, Njiram'madzi, Jenala et al (show 2 more authors) (2018) Safety and Immunogenicity of Seven Dosing Regimens of the Candidate RTS, S/AS01<sub>E</sub> Malaria Vaccine Integrated Within an Expanded Program on Immunization Regimen <i>A Phase II</i>, <i>Single</i>-<i>Center</i>, <i>Open</i>, <i>Controlled Trial in Infants in Malawi</i>. PEDIATRIC INFECTIOUS DISEASE JOURNAL, 37 (5). pp. 483-491.

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Abstract

<h4>Background</h4>In a phase III trial, the RTS,S/AS01 malaria vaccine produced lower anti-circumsporozoite (CS) antibody titers when co-administered with Expanded Programme on Immunization vaccines (0-, 1- and 2-month schedule) at 6 to 12 weeks compared with 5 to 17 months at first vaccination. Alternative infant immunization schedules within the Expanded Programme on Immunization were investigated.<h4>Methods</h4>This phase II, open, single-site (Blantyre, Malawi) trial was conducted in infants 1 to 7 days of age. Subjects were equally randomized across 7 groups to receive 3 doses of RTS,S/AS01E at time points that included ≤7 days, 6, 10, 14 and 26 weeks, and 9 months. All RTS,S/AS01E groups plus a control group (without RTS,S/AS01E) received Bacillus Calmette-Guérin + oral poliovirus vaccine at ≤7 days, diphtheria, tetanus, whole-cell pertussis, hepatitis B and Haemophilus influenzae type b vaccine + oral poliovirus vaccine at 6, 10, and 14 weeks and measles vaccine at 9 months; one RTS,S/AS01E group and the control additionally received hepatitis B vaccination at ≤7 days. Serum anti-CS antibody geometric mean concentration (GMC; enzyme-linked immunosorbent assay) and safety were assessed up to age 18 months.<h4>Results</h4>Of the 480 infants enrolled, 391 completed the study. No causally related serious adverse event was reported. A higher frequency of fever within 7 days of RTS,S/AS01E vaccination compared with control was observed. Compared with the standard 6-, 10-, 14-week schedule, anti-CS antibody GMC ratios post-dose 3 were significantly higher in the 10-, 14- and 26-week group only (ratio 1.80; 95% confidence interval, 1.24-2.60); RTS,S/AS01E vaccination at ≤7 days and 10 and 14 weeks produced significantly lower anti-CS GMCs (ratio 0.59; 95% confidence interval, 0.38-0.92).<h4>Conclusions</h4>Initiation of RTS,S/AS01E vaccination above 6 weeks of age tended to improve anti-CS antibody responses. Neonatal vaccination was well tolerated but produced a comparatively lower immune response.

Item Type: Article
Uncontrolled Keywords: RTS, S/AS01, falciparum, malaria, immunogenicity, neonates
Depositing User: Symplectic Admin
Date Deposited: 05 Mar 2018 07:27
Last Modified: 02 Feb 2024 05:08
DOI: 10.1097/INF.0000000000001937
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3018592
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