BACKGROUND: Patterns of expressed genes in the peripheral blood mononuclear cells of persons who were receiving RTS,S/AS01 or RTS,S/AS02 malaria vaccine and were undergoing experimental challenge with mosquito-borne falciparum malaria were examined to identify markers associated with protection. METHODS: Thirty-nine vaccine recipients were assessed at study entry; on the day of the third vaccination; at 24 h, 72 h, and 2 weeks after vaccination; and on day 5 after challenge. Of 39 vaccine recipients, 13 were protected and 26 were not. Eleven vaccine recipients exhibited delayed onset of parasitemia. All infectivity control subjects developed parasitemia. Prediction analysis of microarrays identified genes corresponding with protection. Gene set enrichment analysis identified sets of genes associated with protection after the third vaccination and before challenge. RESULTS: After the third vaccination and before challenge, differential expression of genes in the immunoproteasome pathway distinguished protected and nonprotected persons. At 5 days after challenge, differential expression of genes associated with programmed cell death distinguished between subjects protected and not protected from malaria blood-stage infection. CONCLUSIONS: The up-regulation of genes associated with the efficient processing of major histocompatibility complex peptides suggests a potential role of the vaccine in conferring major histocompatibility complex class 1-mediated protection and may represent a useful surrogate marker of vaccine efficacy without the need for challenge.
BACKGROUND: Patterns of expressed genes in the peripheral blood mononuclear cells of persons who were receiving RTS,S/AS01 or RTS,S/AS02 malaria vaccine and were undergoing experimental challenge with mosquito-borne falciparum malaria were examined to identify markers associated with protection. METHODS: Thirty-nine vaccine recipients were assessed at study entry; on the day of the third vaccination; at 24 h, 72 h, and 2 weeks after vaccination; and on day 5 after challenge. Of 39 vaccine recipients, 13 were protected and 26 were not. Eleven vaccine recipients exhibited delayed onset of parasitemia. All infectivity control subjects developed parasitemia. Prediction analysis of microarrays identified genes corresponding with protection. Gene set enrichment analysis identified sets of genes associated with protection after the third vaccination and before challenge. RESULTS: After the third vaccination and before challenge, differential expression of genes in the immunoproteasome pathway distinguished protected and nonprotected persons. At 5 days after challenge, differential expression of genes associated with programmed cell death distinguished between subjects protected and not protected from malaria blood-stage infection. CONCLUSIONS: The up-regulation of genes associated with the efficient processing of major histocompatibility complex peptides suggests a potential role of the vaccine in conferring major histocompatibility complex class 1-mediated protection and may represent a useful surrogate marker of vaccine efficacy without the need for challenge.
Authors: Dmitri Kazmin; Helder I Nakaya; Eva K Lee; Matthew J Johnson; Robbert van der Most; Robert A van den Berg; W Ripley Ballou; Erik Jongert; Ulrike Wille-Reece; Christian Ockenhouse; Alan Aderem; Daniel E Zak; Jerald Sadoff; Jenny Hendriks; Jens Wrammert; Rafi Ahmed; Bali Pulendran Journal: Proc Natl Acad Sci U S A Date: 2017-02-13 Impact factor: 11.205
Authors: Joseph R Francica; Daniel E Zak; Caitlyn Linde; Emilio Siena; Carrie Johnson; Michal Juraska; Nicole L Yates; Bronwyn Gunn; Ennio De Gregorio; Barbara J Flynn; Nicholas M Valiante; Padma Malyala; Susan W Barnett; Pampi Sarkar; Manmohan Singh; Siddhartha Jain; Margaret Ackerman; Munir Alam; Guido Ferrari; Andres Salazar; Georgia D Tomaras; Derek T O'Hagan; Alan Aderem; Galit Alter; Robert A Seder Journal: Blood Adv Date: 2017-11-17
Authors: Abdulmohammad Pezeshki; Inna G Ovsyannikova; Brett A McKinney; Gregory A Poland; Richard B Kennedy Journal: Expert Rev Vaccines Date: 2019-02-11 Impact factor: 5.217