Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox

Adamo, Sarah; Gao, Yu; Sekine, Takuya; Mily, Akhirunnesa; Wu, Jinghua; Storgärd, Elisabet; Westergren, Victor; Filén, Finn; Treutiger, Carl-Johan; Sandberg, Johan K.; Sällberg, Matti; Bergman, Peter; Llewellyn-Lacey, Sian; Ljunggren, Hans‐Gustaf; Price, David; Ekström, Anna Mia; Sette, Alessandro; Grifoni, Alba; Buggert, Marcus

doi:10.1016/j.chom.2023.04.015

Cited by 18 publications

(8 citation statements)

References 24 publications

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“…The peptide pools were previously designed based on experimentally defined Orthopox T cell epitopes or predicted T cell epitopes from the most immunodominant ortholog proteins of MPXV; the list of the peptides used in this study has been previously described [29]. It has already been demonstrated that the responses to these peptide pools are associated with VACV-specific T cell responses in a cohort of Dryvax-vaccinated individuals, Jynneos-vaccinated individuals, and MPOX convalescent individuals [29][30][31].…”

Section: Resultsmentioning

confidence: 99%

“…In previous publications, variable percentages (from 0 to about 80%) of responsive T cells upon stimulation with VACV or VACV-derived peptides have been described, and this variability may certainly depend on the laboratory protocol used and the assay selected [12,[17][18][19]21,29,30]. The analysis of the T cell response was restricted to a subset of individuals because of the availability of whole blood samples for PBMC preparation from only 20 vaccinated and 10 unvaccinated participants.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination

Matusali,

Petruccioli,

Cimini

et al. 2023

Vaccines

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When the Mpox virus (MPXV) began spreading globally in 2022, it became critical to evaluate whether residual immunity from smallpox vaccination provided cross-protection. To assess the cross-immune response to MPXV, we collected serum samples (n = 97) and PBMCs (n = 30) from healthy-donors, either born before 1974 and reporting smallpox vaccination during childhood or born after 1975 and not vaccinated with Vaccinia virus (VACV)-based vaccines. We evaluated the levels of anti-MPXV IgG and neutralizing antibodies (Nabs) and the presence of a T cell response against MPXV. We found anti-MPXV IgG and Nabs in 60 (89.6%) and 40 (70.1%) vaccinated individuals, respectively. We observed a T cell response to Orthopoxviruses and MPXV peptide pools in 30% of vaccinated individuals. We thus show that a high proportion of subjects who received the smallpox vaccine 40 to 60 years ago have humoral cross-immunity, while the T-cell-specific response against MPXV was observed in a smaller group (30%) of vaccinated individuals. This study, combined with information on immunity developed during natural infection or the administration of current vaccines, will contribute to a better understanding of humoral and cellular responses against MPXV.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination

Matusali,

Petruccioli,

Cimini

et al. 2023

Vaccines

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“…Recent studies have shown low-level and rapid waning of neutralizing antibodies after MVA-BN (IMVANEX/JYNNEOS) vaccination 25, 26 MVA-BN does not elicit potent maturation of the B-cell repertoire, a critical process for neutralization of the virus and durability of the response 27 , raising the question of the respective roles of B-cell and cellular immunity in vaccine protection. Few studies have investigated T-cell responses against MPXV in humans 28, 29, 30 . Data concerning the quality of immune responses to MPXV and the currently used third generation of MVA-based vaccines are limited 27 .…”

Section: Introductionmentioning

confidence: 99%

Characterization and comparison of immunity against MPXV for individuals infected with MPXV or vaccinated with modified vaccinia Ankara vaccines

Wiedemann,

Surénaud,

Hubert

et al. 2024

Preprint

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The 2022 monkeypox virus (MPXV) outbreak has revitalized questions about immunity against MPXV and vaccinia-based vaccines (VAC-V), but studies are limited. We analyzed immunity against MPXV in individuals infected with MPXV or vaccinated with the licensed modified vaccinia Ankara vaccine (MVA)-BN or an experimental MVA-HIVB vaccine. The frequency of neutralizing antibody (NAb) responders was higher among MPXV-infected individuals than MVA vaccinees. Both MVA vaccines induced similar and strong humoral responses. Similarly, we show a higher frequency and magnitude (5-fold) of T-cell responses, mainly mediated by CD8+ T cells, against a peptide pool containing selected sequences from MPXV, Variola, and VAC-V in MPXV-infected individuals than MVA vaccinees. We describe a hierarchy of cross-reactive T-cell responses against five peptide pools that are highly homologous between VAC-V and MPXV 2022, with the highest frequency of responders against MVA-121L and MVA-018L proteins. Both vaccines stimulated a notable frequency of polyfunctional CD4+ and CD8+ T-cell responses, with a subset of CD4+ T cells showing a mixed cytokine profile. Finally, we found that smallpox vaccination in childhood positively affected humoral but not T-cell vaccine responses, whereas these responses were not affected in people living with HIV. These findings contribute to deciphering and monitoring the profile of immunity to MPXV and MVA. In the context of a potential threat of the reemergence of smallpox following bioterrorism, the diversification and availability of potent vaccines is crucial. The comparable immunogenicity of both MVA vaccines emphasizes the potential utility of MVA-HIVB as a valuable new tool for controlling MPXV outbreaks.

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“…mpox infection and vaccination generally confer robust B-cell and T-cell antibody formation, 21,22 it is unclear how long immunity is conferred. More so, given his low CD4 count, it is expected that his immune function would be altered and lead to suboptimal response.…”

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confidence: 99%

“…More so, given his low CD4 count, it is expected that his immune function would be altered and lead to suboptimal response. 21 Our patient received 2 doses of the JYNNEOS vaccine with the known efficacy of 2 doses in preventing severe mpox infection ranging from 66% to 85% and 35.8% to 86% in patients who received a single dose in immunocompetent patients [23][24][25] ; however, more studies are necessary to address mpox vaccine response in immunocompromised patients. Given these challenges in diagnosis that may lead to delay in care, it is important for clinicians to maintain a high index of suspicion for coinfection in PLWH and immunocompromised patients even in the setting of prior infection and vaccination.…”

mentioning

confidence: 99%

A Case of Varicella Zoster and Mpox Coinfection in a Patient Living With HIV

Mazumder,

Lim,

White

et al. 2024

Sexual Trans Dis

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We present a case of recurrent, cutaneous mpox with co-infection of disseminated varicella zoster in an immunocompromised patient with poorly controlled HIV. This case demonstrates the importance of maintaining a high index of suspicion for mpox despite prior infection and vaccination, as suboptimal immune response is possible in immunocompromised patients, and also noting the potential for co-infection necessitating timely diagnosis and appropriate testing.

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Memory profiles distinguish cross-reactive and virus-specific T cell immunity to mpox

Cited by 18 publications

References 24 publications

Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination

Evaluation of Cross-Immunity to the Mpox Virus Due to Historic Smallpox Vaccination

Characterization and comparison of immunity against MPXV for individuals infected with MPXV or vaccinated with modified vaccinia Ankara vaccines

A Case of Varicella Zoster and Mpox Coinfection in a Patient Living With HIV

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