The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects. As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates.
Here we compare the highly attenuated modified vaccinia virus Ankara (MVA) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA.
Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus
Vaccination with live vaccinia virus affords long-lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia-specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody-mediated depletion of B cells, but not CD4+ or CD8+ T cells, abrogated vaccine-induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long-lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax).
Smallpox DNA vaccine protects nonhuman primates against lethal monkeypox.
Two decades after a worldwide vaccination campaign was used to successfully eradicate naturally occurring smallpox, the threat of bioterrorism has led to renewed vaccination programs. In addition, sporadic outbreaks of human monkeypox in Africa and a recent outbreak of human monkeypox in the U.S. have made it clear that naturally occurring zoonotic orthopoxvirus diseases remain a public health concern. Much of the threat posed by orthopoxviruses could be eliminated by vaccination; however, because the smallpox vaccine is a live orthopoxvirus vaccine (vaccinia virus) administered to the skin, the vaccine itself can pose a serious health risk.
Here, we demonstrate that rhesus macaques vaccinated with a DNA vaccine consisting of four vaccinia virus genes (L1R, A27L, A33R, and B5R) were protected from severe disease after an otherwise lethal challenge with monkeypox virus. Animals vaccinated with a single gene (L1R) which encodes a target of neutralizing antibodies developed severe disease but survived. This is the first demonstration that a subunit vaccine approach to smallpox-monkeypox immunization is feasible.
A tale of two clades: monkeypox viruses
Human monkeypox was first recognized outside Africa in 2003 during an outbreak in the USA that was traced to imported monkeypox virus (MPXV)-infected West African rodents. Unlike the smallpox-like disease described in the Democratic Republic of the Congo (DRC; a Congo Basin country), disease in the USA appeared milder. Here, analyses compared clinical, laboratory and epidemiological features of confirmed human monkeypox case-patients, using data from outbreaks in the USA and the Congo Basin, and the results suggested that human disease pathogenicity was associated with the viral strain.
Genomic sequencing of USA, Western and Central African MPXV isolates confirmed the existence of two MPXV clades. A comparison of open reading frames between MPXV clades permitted prediction of viral proteins that could cause the observed differences in human pathogenicity between these two clades. Understanding the molecular pathogenesis and clinical and epidemiological properties of MPXV can improve monkeypox prevention and control.
Virulence differences between monkeypox virus isolates from West Africa and the Congo basin
Studies indicate that West African and Congo basin isolates of monkeypox virus (MPXV) are genetically distinct. Here, we show Congo basin MPXV-ZAI-V79 is more virulent for cynomolgus monkeys as compared to presumed West African MPXV-COP-58. This finding may explain the lack of case-fatalities in the U.S. 2003 monkeypox outbreak, which was caused by a West African virus. Virulence differences between West African and Congo basin MPXV are further supported by epidemiological analyses that observed a similar prevalence of antibodies in non-vaccinated humans in both regions, while >90% of reported cases occurred in the Congo basin, and no fatal cases were observed outside of this region.
To determine the basis for this difference in virulence, we sequenced the genomes of one human West African isolate, and two presumed West African isolates and compared the sequences to Congo basin MPXV-ZAI-96-I-16. The analysis identified D10L, D14L, B10R, B14R, and B19R as possible virulence genes, with D14L (ortholog of vaccinia complement protein) as a leading candidate.
Outbreak of human monkeypox, Democratic Republic of Congo, 1996 to 1997.
Human monkeypox is a zoonotic smallpox-like disease caused by an orthopoxvirus of interhuman transmissibility too low to sustain spread in susceptible populations. In February 1997, 88 cases of febrile pustular rash were identified for the previous 12 months in 12 villages of the Katako-Kombe Health Zone, Democratic Republic of Congo (attack rate = 22 per 1,000; case-fatality rate = 3.7%). Seven were active cases confirmed by virus isolation. Orthopoxvirus- neutralizing antibodies were detected in 54% of 72 patients who provided serum and 25% of 59 wild-caught animals, mainly squirrels. Hemagglutination-inhibition assays and Western blotting detected antibodies in 68% and 73% of patients, respectively. Vaccinia vaccination, which protects against monkeypox, ceased by 1983 after global smallpox eradication, leading to an increase in the proportion of susceptible people.
Monkeypox B5R |
||
mpv-002 | ProSpec Tany | 100µg |
Monkeypox A33R |
||
mpv-001 | ProSpec Tany | 100µg |
Monkeypox virus |
||
Oneq-VH747-OneqVH747100D | Bioingentech | Oneq-VH747-100D |
Monkeypox virus |
||
Oneq-VH747-OneqVH747150D | Bioingentech | Oneq-VH747-150D |
Monkeypox virus |
||
Oneq-VH747-OneqVH74750D | Bioingentech | Oneq-VH747-50D |
Human Monkeypox Virus Antigen (MPXV) ELISA Kit |
||
abx365123-100g | Abbexa | 100 µg |
Human Monkeypox Virus IgG (MPXV IgG) ELISA Kit |
||
abx092187-100l | Abbexa | 100 µl |
Human Monkeypox Virus IgG (MPXV IgG) ELISA Kit |
||
abx092187-1ml | Abbexa | 1 ml |
Human Monkeypox Virus IgG (MPXV IgG) ELISA Kit |
||
abx092187-200l | Abbexa | 200 µl |
Human Monkeypox Virus IgG (MPXV IgG) ELISA Kit |
||
abx392298-100g | Abbexa | 100 µg |
Human Monkeypox Virus IgM (MPXV IgM) ELISA Kit |
||
abx392299-100g | Abbexa | 100 µg |
Human Monkeypox Virus M1R (MPXV M1R) ELISA Kit |
||
abx395187-50g | Abbexa | 50 µg |
Human Monkeypox Virus H3L (MPXV H3L) ELISA Kit |
||
abx395188-1mg | Abbexa | 1 mg |
Human Monkeypox Virus E8L (MPXV E8L) ELISA Kit |
||
abx395189-1mg | Abbexa | 1 mg |
Human Monkeypox Virus A29L (MPXV A29L) ELISA Kit |
||
abx395186-50g | Abbexa | 50 µg |
Human Monkeypox Virus A35R (MPXV A35R) ELISA Kit |
||
abx395190-1mg | Abbexa | 1 mg |
Human Monkeypox Virus Antigen (MPXV) Rapid Test Kit |
||
abx092162-100l | Abbexa | 100 µl |
Human Monkeypox Virus Antigen (MPXV) Rapid Test Kit |
||
abx092162-1ml | Abbexa | 1 ml |
Human Monkeypox Virus Antigen (MPXV) Rapid Test Kit |
||
abx092162-200l | Abbexa | 200 µl |
Human Monkeypox Virus M1R IgG (MPXV M1R IgG) ELISA Kit |
||
abx395182-100g | Abbexa | 100 µg |
Human Monkeypox Virus H3L IgG (MPXV H3L IgG) ELISA Kit |
||
abx395183-25g | Abbexa | 25 µg |
Human Monkeypox Virus E8L IgG (MPXV E8L IgG) ELISA Kit |
||
abx395184-50g | Abbexa | 50 µg |
Monkeypox Virus, 20 tests/kit |
||
U202028-20 | USTAR Biotechnologies (Hangzhou) | test |
MonkeyPox Virus (MPV) ELISA Kit |
||
SL0026Mk | Sunlong | - |
MonkeyPox Virus (MPV) ELISA Kit |
||
YX-SL0036Mk | Sunlong | - |
Human Monkeypox Virus A29L IgG (MPXV A29L IgG) ELISA Kit |
||
abx395181-50g | Abbexa | 50 µg |
Human Monkeypox Virus A35R IgG (MPXV A35R IgG) ELISA Kit |
||
abx395185-100g | Abbexa | 100 µg |
Recombinant Monkeypox Virus antigen |
||
E41H094 | EnoGene | 100ug |
Recombinant Monkeypox Virus antigen |
||
E41H095 | EnoGene | 100ug |
Human Monkeypox Virus IgG/IgM (MPXV IgG/IgM) Rapid Test Kit |
||
abx092183-100l | Abbexa | 100 µl |
Human Monkeypox Virus IgG/IgM (MPXV IgG/IgM) Rapid Test Kit |
||
abx092183-1ml | Abbexa | 1 ml |
Human Monkeypox Virus IgG/IgM (MPXV IgG/IgM) Rapid Test Kit |
||
abx092183-200l | Abbexa | 200 µl |
Monkeypox Virus Real Time PCR Kit |
||
PDPS-AR064 | Creative Biogene | 1 unit |
Monkeypox Virus Real Time PCR Kit |
||
ZD-0076-01 | Gentaur Genprice | 25 tests/kit |
Monkeypox Virus Real Time PCR Kit |
||
ZD-0076-02 | Gentaur Genprice | 25 tests/kit |
Monkeypox Virus Real Time PCR Kit |
||
YJC70115NW-25T | Jiangsu Bioperfectus Technologies | 25 tests/kit |
Monkeypox Virus (MPXV) RT-PCR Kit |
||
abx471001-1096tests | Abbexa | 10 × 96 tests |
Monkeypox Virus (MPXV) RT-PCR Kit |
||
abx471001-596tests | Abbexa | 5 × 96 tests |
Monkeypox Virus (MPXV) RT-PCR Kit |
||
abx471001-96tests | Abbexa | 96 tests |
Monkeypox Virus (MPXV) E8L ELISA Kit |
||
RK04609 | Abclonal | 96T |
Monkeypox Virus -MPXV- IgG ELISA Kit |
||
E-EL-E620-24Tests | Elabscience Biotech | 24 Tests |
Monkeypox Virus -MPXV- IgG ELISA Kit |
||
E-EL-E620-48Tests | Elabscience Biotech | 48 Tests |
Monkeypox Virus -MPXV- IgG ELISA Kit |
||
E-EL-E620-96Tests | Elabscience Biotech | 96 Tests |
Monkeypox Virus -MPXV- IgG ELISA Kit |
||
E-EL-E620-96Tests10 | Elabscience Biotech | 96 Tests *10 |
Monkeypox Virus -MPXV- IgG ELISA Kit |
||
E-EL-E620-96Tests5 | Elabscience Biotech | 96 Tests *5 |
Monkeypox virus (MPXV) E8L Rabbit mAb |
||
A23087 | Abclonal | 500μL |
Monkeypox Virus E8L (MPXV_USA_2022_MA001), mFc Tag |
||
E24PVA019 | EnoGene | 50 μg |
Monkeypox Virus P4a (MPXV P4a) Protein |
||
abx160093-100g | Abbexa | 100 µg |
Monkeypox Virus P4a (MPXV P4a) Protein |
||
abx160093-10g | Abbexa | 10 µg |
Monkeypox Virus P4a (MPXV P4a) Protein |
||
abx160093-50g | Abbexa | 50 µg |
Monkeypox Virus B5R (MPXV B5R) Protein |
||
abx620096-100g | Abbexa | 100 µg |
Monkeypox Virus B5R (MPXV B5R) Protein |
||
abx620096-1mg | Abbexa | 1 mg |
Monkeypox Virus B5R (MPXV B5R) Protein |
||
abx620096-200g | Abbexa | 200 µg |
Monkeypox Virus H3L (MPXV H3L) Protein |
||
abx620102-100g | Abbexa | 100 µg |
Monkeypox Virus H3L (MPXV H3L) Protein |
||
abx620102-1mg | Abbexa | 1 mg |
Monkeypox Virus H3L (MPXV H3L) Protein |
||
abx620102-200g | Abbexa | 200 µg |
Monkeypox Virus M1R (MPXV M1R) Protein |
||
abx620108-100g | Abbexa | 100 µg |
Monkeypox Virus M1R (MPXV M1R) Protein |
||
abx620108-1mg | Abbexa | 1 mg |
Monkeypox Virus M1R (MPXV M1R) Protein |
||
abx620108-200g | Abbexa | 200 µg |
Monkeypox Virus H3L (MPXV H3L) Protein |
||
abx620112-100g | Abbexa | 100 µg |
Monkeypox Virus H3L (MPXV H3L) Protein |
||
abx620112-1mg | Abbexa | 1 mg |
Monkeypox Virus H3L (MPXV H3L) Protein |
||
abx620112-200g | Abbexa | 200 µg |
Monkeypox Virus M1R (MPXV M1R) Protein |
||
abx620116-100g | Abbexa | 100 µg |
Monkeypox Virus M1R (MPXV M1R) Protein |
||
abx620116-1mg | Abbexa | 1 mg |
Monkeypox Virus M1R (MPXV M1R) Protein |
||
abx620116-200g | Abbexa | 200 µg |
Monkeypox Virus F3L (MPXV F3L) Protein |
||
abx620121-100g | Abbexa | 100 µg |
Monkeypox Virus F3L (MPXV F3L) Protein |
||
abx620121-1mg | Abbexa | 1 mg |
Monkeypox Virus F3L (MPXV F3L) Protein |
||
abx620121-200g | Abbexa | 200 µg |
Monkeypox Virus L1R (MPXV L1R) Protein |
||
abx620122-100g | Abbexa | 100 µg |
Monkeypox Virus L1R (MPXV L1R) Protein |
||
abx620122-1mg | Abbexa | 1 mg |
Monkeypox Virus L1R (MPXV L1R) Protein |
||
abx620122-200g | Abbexa | 200 µg |
Recombinant Monkeypox virus A29 Protein |
||
RP01543 | Abclonal | 100μg |
Recombinant Monkeypox virus L1R Protein |
||
RP01544 | Abclonal | 500μg |
Recombinant Monkeypox virus A29 Protein |
||
RP01546 | Abclonal | 50μg |
Recombinant Monkeypox virus D6L Protein |
||
RP01606 | Abclonal | 50μg |
PCR detection kit for Monkeypox Virus |
||
DA1430 | Daan Gene | 24 test/kit |
Monkeypox Virus H3L (MPXV H3L) Antibody |
||
abx376562-96tests | Abbexa | 96 tests |
Monkeypox Virus M1R (MPXV M1R) Antibody |
||
abx376563-96tests | Abbexa | 96 tests |
Monkeypox Virus M1R (MPXV M1R) Antibody |
||
abx376564-96tests | Abbexa | 96 tests |
Recombinant Monkeypox virus A30L Protein |
||
RP01593 | Abclonal | 20μg |
Recombinant Monkeypox virus B16R Protein |
||
RP01594 | Abclonal | 50μg |
Monkeypox Virus Detection Kit (RT-PCR) |
||
SYNT-RTPCR-24 | Nanjing Synthgene Medical Technology | 24 test/kit |
Monkeypox Virus A33R (MPXV A33R) Protein |
||
abx620095-100g | Abbexa | 100 µg |
Monkeypox Virus A33R (MPXV A33R) Protein |
||
abx620095-1mg | Abbexa | 1 mg |
Monkeypox Virus A33R (MPXV A33R) Protein |
||
abx620095-200g | Abbexa | 200 µg |
Monkeypox Virus D13L (MPXV D13L) Protein |
||
abx620099-100g | Abbexa | 100 µg |
Monkeypox Virus D13L (MPXV D13L) Protein |
||
abx620099-1mg | Abbexa | 1 mg |
Monkeypox Virus D13L (MPXV D13L) Protein |
||
abx620099-200g | Abbexa | 200 µg |
Monkeypox Virus A44R (MPXV A44R) Protein |
||
abx620101-100g | Abbexa | 100 µg |
Monkeypox Virus A44R (MPXV A44R) Protein |
||
abx620101-1mg | Abbexa | 1 mg |
Monkeypox Virus A44R (MPXV A44R) Protein |
||
abx620101-200g | Abbexa | 200 µg |
Monkeypox Virus A26L (MPXV A26L) Protein |
||
abx620104-100g | Abbexa | 100 µg |
Monkeypox Virus A26L (MPXV A26L) Protein |
||
abx620104-1mg | Abbexa | 1 mg |
Monkeypox Virus A26L (MPXV A26L) Protein |
||
abx620104-200g | Abbexa | 200 µg |
Monkeypox Virus A27L (MPXV A27L) Protein |
||
abx620105-100g | Abbexa | 100 µg |
Monkeypox Virus A27L (MPXV A27L) Protein |
||
abx620105-1mg | Abbexa | 1 mg |
Monkeypox Virus A27L (MPXV A27L) Protein |
||
abx620105-200g | Abbexa | 200 µg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx620109-100g | Abbexa | 100 µg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx620109-1mg | Abbexa | 1 mg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx620109-200g | Abbexa | 200 µg |
Monkeypox Virus D14L (MPXV D14L) Protein |
||
abx620111-100g | Abbexa | 100 µg |
Monkeypox Virus D14L (MPXV D14L) Protein |
||
abx620111-1mg | Abbexa | 1 mg |
Monkeypox Virus D14L (MPXV D14L) Protein |
||
abx620111-200g | Abbexa | 200 µg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx620117-100g | Abbexa | 100 µg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx620117-1mg | Abbexa | 1 mg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx620117-200g | Abbexa | 200 µg |
Monkeypox Virus D14L (MPXV D14L) Protein |
||
abx620119-100g | Abbexa | 100 µg |
Monkeypox Virus D14L (MPXV D14L) Protein |
||
abx620119-1mg | Abbexa | 1 mg |
Monkeypox Virus D14L (MPXV D14L) Protein |
||
abx620119-200g | Abbexa | 200 µg |
Monkeypox Virus A14L (MPXV A14L) Protein |
||
abx620120-100g | Abbexa | 100 µg |
Monkeypox Virus A14L (MPXV A14L) Protein |
||
abx620120-1mg | Abbexa | 1 mg |
Monkeypox Virus A14L (MPXV A14L) Protein |
||
abx620120-200g | Abbexa | 200 µg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx645001-100g | Abbexa | 100 µg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx645001-1mg | Abbexa | 1 mg |
Monkeypox Virus A29L (MPXV A29L) Protein |
||
abx645001-200g | Abbexa | 200 µg |
Dynamiker Monkeypox Virus Ag Rapid Test |
||
DNK-2114-1 | Dynamiker Biotechnology | 20 tests |
Monkeypox Virus A29L (MPXV A29L) Antibody |
||
abx376566-96tests | Abbexa | 96 tests |
Monkeypox Virus A29L (MPXV A29L) Antibody |
||
abx345842-100l | Abbexa | 100 µl |
Monkeypox Virus A29L (MPXV A29L) Antibody |
||
abx345842-50l | Abbexa | 50 µl |
Monkeypox-C19L-protein(C-His-tag) |
||
EGPS018D-50 | EnoGene | Monkeypox |
Recombinant Monkeypox Virus M1R Protein [His] |
||
DAG-WT758 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox Virus B6R Protein [His] |
||
DAG-WT761 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox Virus B6R Protein [His] |
||
DAG-WT773 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox Virus H3L Protein [His] |
||
DAG-WT776 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox Virus M1R Protein [His] |
||
DAG-WT779 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox Virus A29L Protein [His] |
||
DAG-WT759 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox Virus A35R Protein [His] |
||
DAG-WT760 | Creative Diagnostics | 1 mg |
Monkeypox Virus Hemagglutinin (MPXV B2R) Protein |
||
abx620100-100g | Abbexa | 100 µg |
Monkeypox Virus Hemagglutinin (MPXV B2R) Protein |
||
abx620100-1mg | Abbexa | 1 mg |
Monkeypox Virus Hemagglutinin (MPXV B2R) Protein |
||
abx620100-200g | Abbexa | 200 µg |
Monkeypox Virus Hemagglutinin (MPXV B2R) Protein |
||
abx620113-100g | Abbexa | 100 µg |
Monkeypox Virus Hemagglutinin (MPXV B2R) Protein |
||
abx620113-1mg | Abbexa | 1 mg |
Monkeypox Virus Hemagglutinin (MPXV B2R) Protein |
||
abx620113-200g | Abbexa | 200 µg |
Recombinant Monkeypox virus A33R protein (His tag) |
||
PDEV100007-100ug | Elabscience Biotech | 100ug |
Recombinant Monkeypox virus A33R protein (His tag) |
||
PDEV100007-20ug | Elabscience Biotech | 20ug |
Recombinant Monkeypox Virus Chimeric Protein (B21R&A29L) |
||
DAG-WT764 | Creative Diagnostics | 1 mg |
Recombinant Monkeypox virus A26L protein (His,SUMO tag) |
||
PDEV100008-100ug | Elabscience Biotech | 100ug |
Recombinant Monkeypox virus A26L protein (His,SUMO tag) |
||
PDEV100008-20ug | Elabscience Biotech | 20ug |
Recombinant Monkeypox virus MPXV(A29L) protein (His tag) |
||
PDEV100009-100ug | Elabscience Biotech | 100ug |
Recombinant Monkeypox virus MPXV(A29L) protein (His tag) |
||
PDEV100009-20ug | Elabscience Biotech | 20ug |
Monkeypox Virus A5L and A11L (MPXV A5L-A11L) Protein |
||
abx160091-100g | Abbexa | 100 µg |
Monkeypox Virus A5L and A11L (MPXV A5L-A11L) Protein |
||
abx160091-10g | Abbexa | 10 µg |
Monkeypox Virus A5L and A11L (MPXV A5L-A11L) Protein |
||
abx160091-50g | Abbexa | 50 µg |
Monkeypox Virus Envelope Protein F13 (MPXV C19L) Protein |
||
abx620098-100g | Abbexa | 100 µg |
Monkeypox Virus Envelope Protein F13 (MPXV C19L) Protein |
||
abx620098-1mg | Abbexa | 1 mg |
Monkeypox Virus Envelope Protein F13 (MPXV C19L) Protein |
||
abx620098-200g | Abbexa | 200 µg |
Mouse Anti Monkeypox Virus E8L Monoclonal Clone SAA0285 |
||
IMSAMPXVE8LSAA0285C100UG | Innovative research | each |
×
Human monkeypox: an emerging zoonosis.
Human monkeypox is a rare viral zoonosis endemic to central and western Africa that has recently emerged in the USA. Laboratory diagnosis is important because the virus can cause disease that is clinically indistinguishable from other pox-like illnesses, particularly smallpox and chickenpox. Although the natural animal reservoir of the monkeypox virus is unknown, rodents are the probable source of its introduction into the USA. A clear understanding of the virulence and transmissibility of human monkeypox has been limited by inconsistencies in epidemiological investigations. Monkeypox is the most important orthopoxvirus infection in human beings since the eradication of smallpox in the 1970s. There is currently no proven treatment for human monkeypox, and questions about its potential as an agent of bioterrorism persist.