TY - JOUR
T1 - Mpox vaccine and infection-driven human immune signatures
T2 - an immunological analysis of an observational study
AU - Cohn, Hallie
AU - Bloom, Nathaniel
AU - Cai, Gianna Y.
AU - Clark, Jordan J.
AU - Tarke, Alison
AU - Bermúdez-González, Maria C.
AU - Altman, Deena R.
AU - Lugo, Luz Amarilis
AU - Lobo, Francisco Pereira
AU - Marquez, Susanna
AU - Amoako, Angela
AU - Andre, Dalles
AU - van Bakel, Harm
AU - Cognini, Christian C.
AU - Gleason, Charles
AU - Gonzales-Reiche, Ana
AU - van Kesteren, Morgan
AU - Kleiner, Giulio
AU - Lyttle, Neko
AU - Mauldin, Jacob D.
AU - Monahan, Brian C.
AU - Nardulli, Jessica R.
AU - Oostenink, Annika
AU - Paniz-Mondolfi, Alberto
AU - Polanco, Jose
AU - Ramírez, Juan David
AU - Rooker, Aria
AU - Sordillo, Emilia Mia
AU - Srivastava, Komal
AU - Chen, Jin Qiu
AU - Ren, Wenlin
AU - Qin, Lili
AU - Yates, Jennifer L.
AU - Hunt, Danielle T.
AU - Lee, William T.
AU - Crotty, Shane
AU - Krammer, Florian
AU - Grifoni, Alba
AU - Sette, Alessandro
AU - Simon, Viviana
AU - Coelho, Camila H.
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/11
Y1 - 2023/11
N2 - Background: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. Methods: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. Findings: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6–33 days after the first dose and 5–40 days after the second dose. Mpox-convalescent samples were collected 20–102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20–102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. Interpretation: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. Funding: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.
AB - Background: Monkeypox virus has recently infected more than 88 000 people, raising concerns about our preparedness against this emerging viral pathogen. Licensed and approved for mpox, the JYNNEOS vaccine has fewer side-effects than previous smallpox vaccines and has shown immunogenicity against monkeypox in animal models. This study aims to elucidate human immune responses to JYNNEOS vaccination compared with mpox-induced immunity. Methods: Peripheral blood mononuclear cells and sera were obtained from ten individuals vaccinated with one or two doses of JYNNEOS and six individuals diagnosed with monkeypox virus infection. Samples were obtained from seven individuals before vaccination to serve as a baseline. We examined the polyclonal serum (ELISA) and single B-cell (heavy chain gene and transcriptome data) antibody repertoires and T-cell responses (activation-induced marker and intracellular cytokine staining assays) induced by the JYNNEOS vaccine versus monkeypox virus infection. Findings: All participants were men between the ages of 21 and 60 years, except for one woman in the group of mpox-convalescent individuals, and none had previous orthopoxvirus exposure. All mpox cases were mild. Vaccinee samples were collected 6–33 days after the first dose and 5–40 days after the second dose. Mpox-convalescent samples were collected 20–102 days after infection. In vaccine recipients, gene-level plasmablast and antibody responses were negligible and sera displayed moderate binding to recombinant orthopoxviral proteins (A29L, A35R, E8L, A30L, A27L, A33R, B18R, and L1R) and native proteins from the 2022 monkeypox outbreak strain. By contrast, recent monkeypox virus infection (within 20–102 days) induced robust serum antibody responses to monkeypox virus proteins and to native monkeypox virus proteins from a viral isolate obtained during the 2022 outbreak. JYNNEOS vaccine recipients presented robust orthopoxviral CD4+ and CD8+ T-cell responses. Interpretation: Infection with monkeypox virus resulted in robust B-cell and T-cell responses, whereas immunisation with JYNNEOS elicited more robust T-cell responses. These data can help to inform vaccine design and policies for preventing mpox in humans. Funding: National Cancer Institute (National Institutes of Health), National Institute of Allergy and Infectious Diseases (National Institutes of Health), and Icahn School of Medicine.
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U2 - 10.1016/S1473-3099(23)00352-3
DO - 10.1016/S1473-3099(23)00352-3
M3 - Research Article
C2 - 37475115
AN - SCOPUS:85168737591
SN - 1473-3099
VL - 23
SP - 1302
EP - 1312
JO - The Lancet Infectious Diseases
JF - The Lancet Infectious Diseases
IS - 11
ER -