Effectiveness of one dose of MVA-BN smallpox vaccine against monkeypox in England using the case-coverage method

Bertran, Marta; Andrews, Nick; Davison, Chloe; Dugbazah, Bennet; Boateng, Jacob; Lunt, Rachel; Hardstaff, Joanne; Green, Melanie; Blomquist, Paula; Turner, Charlie; Mohammed, Hamish; Cordery, Rebecca; Mandal, Sema; Campbell, Colin; Ladhani, Shamez; Ramsay, Mary; Amirthalingam, Gayatri

doi:10.1101/2022.12.13.22282654

Cited by 13 publications

(13 citation statements)

References 16 publications

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“…Nevertheless, a lack of robust antibody responses after one dose of IMVANEX in previously unvaccinated individuals (aged <50) does not suggest a lack of protection, as recent studies have shown that vaccine efficacy against disease after one dose of IMVANEX has been suggested to be as high as 78% when comparing vaccinated with unvaccinated individuals 45 .…”

Section: Monkeypox-convalescent Individualsmentioning

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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Section: Monkeypox-convalescent Individualsmentioning

confidence: 99%

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

Otter¹,

Jones²,

Hicks³

et al. 2022

Preprint

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“…3 Studies from this recent outbreak reported 9–18% vaccinated participants. 4,5 Smallpox Vaccinia virus-based (VACV) vaccines induce cross-protection against symptoms caused by other orthopoxviruses, including Mpox, 6–10 but vaccination at childhood does not necessarily provide robust neither permanent immunity against Mpox 11 as is suggested in our patient. Specific memory CD4 + and CD8 + T cells, B cells and antibodies were found to persist >50 years following VACV vaccine.…”

Section: Discussionmentioning

confidence: 69%

Suspected case of monkeypox reinfection versus reactivation in a immunocompetent patient, Barcelona, 2022

et al. 2023

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Vaccines against smallpox are known to have cross-protective activity against monkeypox, and smallpox and monkeypox infections are believed to generate permanent immunity. Nevertheless, there are scarce data about the possibility of reinfection or reactivation. Recently, a case of apparent monkeypox reinfection has been reported. We present a suspected case of second episode of monkeypox in a healthy and previously vaccinated man, with a confirmed primary monkeypox infection occurring three months before the second confirmed presentation.

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“…Two studies based on aggregated data conducted in the United States [16,17] in males 18-49 years old at risk of mpox, found a risk of MPXV infection more than 7 times higher in the unvaccinated compared to the vaccinated, which would be equivalent to an 86% protection conferred by the vaccine. One study in the United Kingdom [15] using the screening method [29] found a vaccine effectiveness of 78% starting 14 days after a single dose. Two studies in the United States, using case-control designs, have provided discordant estimates of VE with one dose of 75% [19] or 36% [18](72% and 41% in immunocompetent individuals, respectively), likely due to differences in the selection criteria for both cases and controls.…”

Section: Discussionmentioning

confidence: 99%

“…Before the current outbreak, no estimates of clinical efficacy were available outside of animal models [13,14]. During the outbreak, estimates of vaccine effectiveness (VE), when administered pre-exposure, have been produced by the United Kingdom [15], the United States [16][17][18][19] and Israel [20], though only the latter was a cohort study, and had some methodological limitations [21]. The greatest difficulty for individual-based mpox VE studies has been the lack of a sampling frame of the population targeted for vaccination, needed to identify vaccinated and unvaccinated groups that are similar in risk practices and risk of mpox virus (MPXV) infection, independently of the probability of receiving a dose of MVA-BN vaccine.…”

Section: Introductionmentioning

confidence: 99%

Reduction in the risk of mpox infection after MVA-BN vaccination in individuals on HIV pre-exposure prophylaxis: a Spanish cohort study

Fontán-Vela,

Hernando,

Olmedo

et al. 2023

Preprint

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Objectives: To assess the effectiveness of at least one-dose of the Modified Vaccinia Ankara-Bavaria Nordic (MVA-BN) smallpox vaccine, administered pre-exposure, against mpox virus (MPXV) infection in persons receiving pre-exposure prophylaxis for HIV (HIV-PrEP). Design: Retrospective cohort, constructed by deterministic linkage of electronic health records. Setting: 15 of 19 regions in Spain (>95% population), between July 12 and December 12, 2022 Participants: Men >=18 years, receiving HIV-PrEP as of July 12 and with no previous MPXV infection or vaccination against mpox. Interventions: On each day, we matched individuals receiving a first dose of MVA-BN vaccine pre-exposure and unvaccinated controls of the same age (minus/plus 5 years) and region. Main outcome measures: We estimated the risk of laboratory-confirmed infection with MPXV using a Kaplan-Meier estimator and calculated risk ratios (RR) and vaccine effectiveness (VE=1-RR). Results: We included 5,660 matched pairs, with a median follow-up of 62 days (interquartile range 24-97). Mpox cumulative incidence was 5.6 per 1,000 (25 cases) in unvaccinated and 3.5 per 1,000 (18 cases) in vaccinated; last case occurred at 63 and 17 days after enrolment, respectively. No effect was found during days 0-6 post-vaccination (VE -38.3; 95% confidence interval (95%CI): -332.7; 46.4), but VE was 65% in ≥7 days (95%CI 22.9; 88.0) and 79% in ≥14 days (95%CI 33.3; 100.0) after vaccination. Conclusion: At least one dose of MVA-BN vaccine offered protection against mpox in a most-at-risk population. Because the incidence of mpox was decreasing shortly after the vaccination campaign began, we can only assess its effectiveness shortly after vaccination. Further studies need to assess the VE of a second dose and the duration of protection over time.

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Effectiveness of one dose of MVA-BN smallpox vaccine against monkeypox in England using the case-coverage method

Cited by 13 publications

References 16 publications

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

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

Suspected case of monkeypox reinfection versus reactivation in a immunocompetent patient, Barcelona, 2022

Reduction in the risk of mpox infection after MVA-BN vaccination in individuals on HIV pre-exposure prophylaxis: a Spanish cohort study

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