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

Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, Paolino K, Moon J, Komisar J, Kamau E, Oliver T, Chhoeu A, Murphy J, Lyke K, Laurens M, Birkett A, Lee C, Weltzin R, Wille-Reece U, Sedegah M, Hendriks J, Versteege I, Pau MG, Sadoff J, Vanloubbeeck Y, Lievens M, Heerwegh D, Moris P, Guerra Mendoza Y, Jongert E, Cohen J, Voss G, Ballou WR, Vekemans J - PLoS ONE (2015)

Bottom Line: The RRR-group had greater anti-CS specific IgG titers than did the ARR-group.An 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.

View Article: PubMed Central - PubMed

Affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.

ABSTRACT

Methods: In 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.

Results: ARR 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).

Conclusions: An 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 registration: ClinicalTrials.gov NCT01366534.

No MeSH data available.


Related in: MedlinePlus

Flow diagram.The number of subjects completing each immunization and controlled human malaria infection. ARR = first dose with Ad35.CS, second and third doses with RTS,S/AS01B. RRR = three doses of RTS,S/AS01B
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pone.0131571.g001: Flow diagram.The number of subjects completing each immunization and controlled human malaria infection. ARR = first dose with Ad35.CS, second and third doses with RTS,S/AS01B. RRR = three doses of RTS,S/AS01B

Mentions: This was an observer-blind, randomized Phase 2a study in healthy malaria-naïve adults designed to evaluate safety, reactogenicity, immunogenicity, and efficacy of Ad35.CS.01 followed by two doses of RTS,S/AS01 (ARR group) compared to three doses of RTS,S/AS01 (RRR group) (www.clinicaltrials.gov NCT01366534; Fig 1), conducted at the Walter Reed Army Institute of Research (WRAIR) between August 2011 and July 2012. Vaccination and challenge were to be performed in three sequential cohorts (Cohorts A, B and C). Each cohort to be vaccinated was to include approximately 56 subjects of which a random selection of subjects eligible for challenge was done to ensure that a maximum of 46 vaccinated individuals progressed to the challenge phase, given logistical constraints. Eligibility criteria are presented in S1 Text available with this manuscript. The results in this paper refer only to those in Cohort A as pre-defined criteria to progress to cohort B and C were not met.


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

Ockenhouse CF, Regules J, Tosh D, Cowden J, Kathcart A, Cummings J, Paolino K, Moon J, Komisar J, Kamau E, Oliver T, Chhoeu A, Murphy J, Lyke K, Laurens M, Birkett A, Lee C, Weltzin R, Wille-Reece U, Sedegah M, Hendriks J, Versteege I, Pau MG, Sadoff J, Vanloubbeeck Y, Lievens M, Heerwegh D, Moris P, Guerra Mendoza Y, Jongert E, Cohen J, Voss G, Ballou WR, Vekemans J - PLoS ONE (2015)

Flow diagram.The number of subjects completing each immunization and controlled human malaria infection. ARR = first dose with Ad35.CS, second and third doses with RTS,S/AS01B. RRR = three doses of RTS,S/AS01B
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492580&req=5

pone.0131571.g001: Flow diagram.The number of subjects completing each immunization and controlled human malaria infection. ARR = first dose with Ad35.CS, second and third doses with RTS,S/AS01B. RRR = three doses of RTS,S/AS01B
Mentions: This was an observer-blind, randomized Phase 2a study in healthy malaria-naïve adults designed to evaluate safety, reactogenicity, immunogenicity, and efficacy of Ad35.CS.01 followed by two doses of RTS,S/AS01 (ARR group) compared to three doses of RTS,S/AS01 (RRR group) (www.clinicaltrials.gov NCT01366534; Fig 1), conducted at the Walter Reed Army Institute of Research (WRAIR) between August 2011 and July 2012. Vaccination and challenge were to be performed in three sequential cohorts (Cohorts A, B and C). Each cohort to be vaccinated was to include approximately 56 subjects of which a random selection of subjects eligible for challenge was done to ensure that a maximum of 46 vaccinated individuals progressed to the challenge phase, given logistical constraints. Eligibility criteria are presented in S1 Text available with this manuscript. The results in this paper refer only to those in Cohort A as pre-defined criteria to progress to cohort B and C were not met.

Bottom Line: The RRR-group had greater anti-CS specific IgG titers than did the ARR-group.An 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.

View Article: PubMed Central - PubMed

Affiliation: Walter Reed Army Institute of Research, Silver Spring, MD, United States of America.

ABSTRACT

Methods: In 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.

Results: ARR 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).

Conclusions: An 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 registration: ClinicalTrials.gov NCT01366534.

No MeSH data available.


Related in: MedlinePlus