Retrospective Proteomic Analysis of Serum After Akhmeta Virus Infection: New Suspect Case Identification and Insights Into Poxvirus Humoral Immunity

Townsend, Michael; Gallardo-Romero, Nadia; Khmaladze, Ekaterine; Vora, Neil M.; Maghlakelidze, Giorgi; Geleishvili, Marika; Carroll, Darin S.; Emerson, Ginny L.; Reynolds, Mary G.; Satheshkumar, Panayampalli S.

doi:10.1093/infdis/jix534

Cited by 6 publications

(3 citation statements)

References 20 publications

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“…However, the low incidence of MPXV infection, low human-to-human transmission, and the observation that MPX is an acute rather than persistent infection makes superinfection or co-infection with VARV unlikely. While these speculations cannot be examined experimentally due to ethical consideration and dual use risk [201], analysis of historical/retrospective samples by using next generation sequencing and proteomic technologies [202,203] will shed light on the role of co-infection/superinfection, recombination and preexisting MPXV antibodies to VARV and MPXV infection biology. These studies are essential to our understanding of the host and viral factors that modulate MPXV pathogenesis and its possible emergence as a VARV-like pathogen.…”

Section: Co-infection and Recombinationmentioning

confidence: 99%

Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution

Alakunle

Moens

Nchinda

et al. 2020

Viruses

582

685

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Monkeypox is a zoonotic disease caused by monkeypox virus (MPXV), which is a member of orthopoxvirus genus. The reemergence of MPXV in 2017 (at Bayelsa state) after 39 years of no reported case in Nigeria, and the export of travelers’ monkeypox (MPX) from Nigeria to other parts of the world, in 2018 and 2019, respectively, have raised concern that MPXV may have emerged to occupy the ecological and immunological niche vacated by smallpox virus. This review X-rays the current state of knowledge pertaining the infection biology, epidemiology, and evolution of MPXV in Nigeria and worldwide, especially with regard to the human, cellular, and viral factors that modulate the virus transmission dynamics, infection, and its maintenance in nature. This paper also elucidates the role of recombination, gene loss and gene gain in MPXV evolution, chronicles the role of signaling in MPXV infection, and reviews the current therapeutic options available for the treatment and prevention of MPX. Additionally, genome-wide phylogenetic analysis was undertaken, and we show that MPXV isolates from recent 2017 outbreak in Nigeria were monophyletic with the isolate exported to Israel from Nigeria but do not share the most recent common ancestor with isolates obtained from earlier outbreaks, in 1971 and 1978, respectively. Finally, the review highlighted gaps in knowledge particularly the non-identification of a definitive reservoir host animal for MPXV and proposed future research endeavors to address the unresolved questions.

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Section: Co-infection and Recombinationmentioning

confidence: 99%

Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution

Alakunle

Moens

Nchinda

et al. 2020

Viruses

582

685

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“…To limit transmission during the 2022 MPXV outbreak, public health agencies recommend Smallpox vaccination, as previous studies have shown protection from MPOX disease using the Smallpox vaccines such as IMVANEX or ACAM2000 [27][28][29][30][31] . The immunology of Dryvax®, ACAM2000 and IMVANEX vaccines has been well studied 27,[32][33][34][35][36] , with antibody responses detected up to 35 years post-Smallpox vaccination 34 . However, studying the immunology to MPXV infection and disease has been limited by the geographical distribution, limited number of human cases worldwide and access to convalescent serum samples.…”

Section: Introductionmentioning

confidence: 99%

Analogous humoral antigen recognition between Monkeypox-infected and Smallpox-vaccinated individuals

Otter¹,

Jones²,

Hicks³

et al. 2022

Preprint

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In early 2022, a cluster of Monkeypox (now termed MPOX) virus (MPXV) cases were identified within the UK with no prior travel history to MPXV-endemic regions, suggesting localised transmission of MPXV within the UK. Subsequently, cases were identified in several other non-endemic countries and currently exceed 80,000 worldwide, primarily affecting gay, bisexual, and other men who have sex with men. Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISA assays to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with one, two, or three doses of IMVANEX or ACAM2000 (Modified Vaccinia Ankara (MVA)) vaccination, and those with prior MPOX infection were tested against these antigens, with Pearson correlation, principal component analysis and receiver operator curve statistics used to further elucidate antigenic responses to pox-virus infection. Furthermore, using our data, we demonstrated the development of a pooled antigen ELISA that can reliably detect antibody responses induced by Smallpox vaccination or MPXV infection. Using diverse poxvirus antigen ELISAs, we observe that one dose of Smallpox vaccination induces a low number of antibodies, primarily against MPXV B2, with a second dose inducing considerably higher antibody responses against B2R but also to other MPXV antigens such as B5, E8, M1, and A35. Prior MPXV infection, both Clades IIa and IIb, induce variable responses, but similarly induce antibody responses to poxvirus antigens observed in Smallpox-vaccinated individuals, and additionally responses to MPXV A27, A29 and H3. Principal component and Pearson correlation matrix identified MPXV A27 as a differential between IMVANEX and MPOX-infected individuals, whilst MPXV M1 (VACV L1) is likely a serological marker of IMVANEX-vaccination. When using recombinant MPXV/VACV protein homologues, we also observe a difference in antigen binding, with variability based on the individual's originating infection/vaccination. Using a pooled-antigen ELISA, we also demonstrate a sensitivity of 97.14% (95% CI:91.93-99.22) and specificity of 98.23% (96.67-99.07) in detecting poxvirus antibodies with applicability to measuring longitudinal antibody responses post-vaccination/post-MPXV infection. Here, we show that both MPXV-infected or Smallpox-vaccinated individuals mount antibodies able to bind a diverse but core set of poxvirus antigens, with implications for future vaccine (e.g., mRNA-based) and therapeutic (e.g., monoclonal antibodies) targets. We identify low levels of antibodies observed in those post-dose one IMVANEX, but considerably higher levels of antibodies post-dose two. We also demonstrate that homologous VACV and MPXV antigens may offer a mechanism for discriminating between vaccinated and MPXV-infected individuals through differential binding, aiding in serosurveillance and future immunology studies.

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“…To limit transmission during the 2022 MPXV outbreak, public health agencies recommend Smallpox vaccination, as previous studies have shown protection from Mpox disease using Smallpox vaccines such as IMVANEX or ACAM2000 27 – 31 . The immunology of Dryvax®, ACAM2000 and IMVANEX vaccines has been well studied 27 , 32 – 36 , with antibody responses detected up to 35 years post-Smallpox vaccination 34 . However, studying the immunology to MPXV infection and disease has been limited by the geographical distribution, limited number of human cases worldwide and access to convalescent serum samples.…”

Section: Introductionmentioning

confidence: 99%

Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals

Otter,

Jones,

Hicks

et al. 2023

Nat Commun

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In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.

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Retrospective Proteomic Analysis of Serum After Akhmeta Virus Infection: New Suspect Case Identification and Insights Into Poxvirus Humoral Immunity

Cited by 6 publications

References 20 publications

Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution

Monkeypox Virus in Nigeria: Infection Biology, Epidemiology, and Evolution

Analogous humoral antigen recognition between Monkeypox-infected and Smallpox-vaccinated individuals

Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals

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