Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults

Caroline Ogwang, Muhammed Afolabi, Domtila Kimani, Ya Jankey Jagne, Susanne H Sheehy, Carly M Bliss, Christopher J A Duncan, Katharine A Collins, Miguel A Garcia Knight, Eva Kimani, Nicholas A Anagnostou, Eleanor Berrie, Sarah Moyle, Sarah C Gilbert, Alexandra J Spencer, Peninah Soipei, Jenny Mueller, Joseph Okebe, Stefano Colloca, Riccardo Cortese, Nicola K Viebig, Rachel Roberts, Katherine Gantlett, Alison M Lawrie, Alfredo Nicosia, Egeruan B Imoukhuede, Philip Bejon, Britta C Urban, Katie L Flanagan, Katie J Ewer, Roma Chilengi, Adrian V S Hill, Kalifa Bojang, Caroline Ogwang, Muhammed Afolabi, Domtila Kimani, Ya Jankey Jagne, Susanne H Sheehy, Carly M Bliss, Christopher J A Duncan, Katharine A Collins, Miguel A Garcia Knight, Eva Kimani, Nicholas A Anagnostou, Eleanor Berrie, Sarah Moyle, Sarah C Gilbert, Alexandra J Spencer, Peninah Soipei, Jenny Mueller, Joseph Okebe, Stefano Colloca, Riccardo Cortese, Nicola K Viebig, Rachel Roberts, Katherine Gantlett, Alison M Lawrie, Alfredo Nicosia, Egeruan B Imoukhuede, Philip Bejon, Britta C Urban, Katie L Flanagan, Katie J Ewer, Roma Chilengi, Adrian V S Hill, Kalifa Bojang

Abstract

Background: Heterologous prime boost immunization with chimpanzee adenovirus 63 (ChAd63) and Modified vaccinia Virus Ankara (MVA) vectored vaccines is a strategy recently shown to be capable of inducing strong cell mediated responses against several antigens from the malaria parasite. ChAd63-MVA expressing the Plasmodium falciparum pre-erythrocytic antigen ME-TRAP (multiple epitope string with thrombospondin-related adhesion protein) is a leading malaria vaccine candidate, capable of inducing sterile protection in malaria naïve adults following controlled human malaria infection (CHMI).

Methodology: We conducted two Phase Ib dose escalation clinical trials assessing the safety and immunogenicity of ChAd63-MVA ME-TRAP in 46 healthy malaria exposed adults in two African countries with similar malaria transmission patterns.

Results: ChAd63-MVA ME-TRAP was shown to be safe and immunogenic, inducing high-level T cell responses (median >1300 SFU/million PBMC).

Conclusions: ChAd63-MVA ME-TRAP is a safe and highly immunogenic vaccine regimen in adults with prior exposure to malaria. Further clinical trials to assess safety and immunogenicity in children and infants and protective efficacy in the field are now warranted.

Trial registration: Pactr.org PACTR2010020001771828 Pactr.org PACTR201008000221638 ClinicalTrials.gov NCT01373879 NCT01373879 ClinicalTrials.gov NCT01379430 NCT01379430.

Conflict of interest statement

Competing Interests: AH is a named inventor on the following patent applications on malaria vectored vaccines and immunization regimes (WO2008/122769, Adenoviral vector encoding malaria antigen; and WO 2008/122811 Novel adenovirus vectors). Authors from Okairòs are employees of and/or shareholders in Okairòs, which is developing vectored vaccines for malaria and other diseases. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Clinical Trial Designs.
Figure 1. Clinical Trial Designs.
Trial A = Phase Ib clinical trial in The Gambia, West Africa. Trial B = Phase Ib clinical trial in Kilifi, Kenya, East Africa. IM = intramuscular administration. ID = intradermal administration. In Trial A, 10 volunteers were excluded following screening for the following reasons: severe thrombocytopenia, severe proteinuria, spastic deformity of arm and withdrawal of consent (seven individuals). In Trial B, 14 volunteers were excluded following screening for the following reasons: hypertension (two individuals), positive serology for HIV (two individuals), positive Hepatitis B surface antigen (four individuals), participation in a previous malaria vaccine trial (2 individuals), peptic ulcer disease, allergic disease, recruitment complete (one participant).
Figure 2. Local and systemic AEs deemed…
Figure 2. Local and systemic AEs deemed definitely, probably or possibly related to ChAd63 ME-TRAP.
Only the highest intensity of each AE per subject is listed. Data are combined for all AEs for all volunteers receiving the same vaccine at the stated dose. There were no immunization related serious AEs. IM = intramuscular. (A) Local AEs post ChAd63 ME-TRAP. (B) Systemic AEs post ChAd63 ME-TRAP.
Figure 3. Local and systemic AEs deemed…
Figure 3. Local and systemic AEs deemed definitely, probably or possibly related to MVA ME-TRAP.
Only the highest intensity of each AE per subject is listed. Data are combined for all AEs for all volunteers receiving the same vaccine at the stated dose. There were no immunization related serious AEs. IM = intramuscular. ID = Intradermal. (A) Local AEs post MVA ME-TRAP. (B) Systemic AEs post MVA ME-TRAP.
Figure 4. IFN-γ ELISPOT responses to ChAd63-MVA…
Figure 4. IFN-γ ELISPOT responses to ChAd63-MVA ME-TRAP.
(A) Time course of IFN-γ ELISPOT responses to ChAd63-MVA ME-TRAP. Lines show median immune response to high dose (solid line) and lower dose (dashed line) of ChAd63 ME-TRAP in Trial A (grey line) and Trial B (black line). For Trial B medians are for groups with MVA given IM and ID combined. (B) Peak immune response (day 63–7 days post MVA vaccination) to ChAd63 and MVA ME-TRAP stratified by route of administration of MVA, dose of ChAd63 and trial site. Bar represents geometric mean. Circles represent MVA given IM, squares represent MVA given ID. Closed symbols represent 1×1010 vp ChAd63 and open symbols 5×1010 vp ChAd63.

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