Ad35.CS.01 - RTS,S/AS01 Heterologous Prime Boost Vaccine Efficacy against Sporozoite Challenge in Healthy Malaria-Naïve Adults

Abstract

MethodsIn an observer blind, phase 2 trial, 55 adults were randomized to receive one dose of Ad35.CS.01 vaccine followed by two doses of RTS,S/AS01 (ARR-group) or three doses of RTS,S/AS01 (RRR-group) at months 0, 1, 2 followed by controlled human malaria infection.ResultsARR and RRR vaccine regimens were well tolerated. Efficacy of ARR and RRR groups after controlled human malaria infection was 44% (95% confidence interval 21%-60%) and 52% (25%-70%), respectively. The RRR-group had greater anti-CS specific IgG titers than did the ARR-group. There were higher numbers of CS-specific CD4 T-cells expressing > 2 cytokine/activation markers and more ex vivo IFN-γ enzyme-linked immunospots in the ARR-group than the RRR-group. Protected subjects had higher CS-specific IgG titers than non-protected subjects (geometric mean titer, 120.8 vs 51.8 EU/ml, respectively; P = .001).ConclusionsAn increase in vaccine efficacy of ARR-group over RRR-group was not achieved. Future strategies to improve upon RTS,S-induced protection may need to utilize alternative highly immunogenic prime-boost regimens and/or additional target antigens.Trial RegistrationClinicalTrials.gov NCT01366534

Systems analysis of protective immune responses to RTS,S malaria vaccination in humans

“…The magnitude of the CSP-specific antibody responses induced by RTS,S/AS01 vaccination has been correlated with protection in previous studies (18). However, RTS,S/AS01 vaccination does not induce CD8…”

“…The clinical trial (NCT01366534) was conducted at Walter Reed Army Institute of Research, as described (18). Forty-six healthy malarianaïve volunteers, randomized to two study arms, participated in this study testing the efficacy of RTS,S and AdVac malaria vaccine candidates ( Fig.…”

“…Forty-six healthy malarianaïve volunteers, randomized to two study arms, participated in this study testing the efficacy of RTS,S and AdVac malaria vaccine candidates ( Fig. 1), as described (18). Study arm 1 (hereafter referred to as ARR), comprised of 25 volunteers who received the AdVac vaccine composed of Ad35 vector expressing full-length CSP, as a primary immunization, was followed by two doses of RTS, S/AS01 vaccine.…”

“…Recently, an Ad35-CSP (AdVac)-RTS, S/AS01 prime-boost approach was tested in humans, and its efficacy and immunogenicity was compared with the RTS,S/AS01 vaccine candidate alone (18). Surprisingly, however, inclusion of the adenoviral prime immunization did not result in increased vaccine efficacy (18).…”

Development of Vaccines Based on Adenoviral Vectors: A Review of Foreign Clinical Studies (Part 2)

“…В схеме прайм-буст вакцинации Ad35.CS.01/GSK257049 предварительное введение аденовектора не обе-спечивало развитие более значительной защиты добровольцев от заражения малярийным плаз-модием по сравнению с режимом трехкратных инъекций вакцины GSK. При этом уровень Т-клеточного иммунного ответа в группе, полу-чившей инъекцию аденовирусного вектора, был более высоким [17]. Результаты еще одного ис-следования не опубликованы.…”