Monkeypox Vaccine Research

Authored by
Last reviewed
August 16, 2022

Monkeypox Vaccine Clinical Research

The worldwide monkeypox virus (MPXV) outbreak in 2022 is approaching a pandemic-level impact on society. To better understand the protection offered by U.S. FDA-approved Jynneos and ACM2000 vaccines, various clinical researchers at the U.S. NIH, UKHSA, WHO, and others have published peer-reviewed information offering keen insights as of August 5, 2022.

The U.S. White House Office of Science and Technology Policy (OSTP) announced on August 4, 2022, a coordinated call to action with science and technology leaders and advisors asking scholarly publishers to make all monkeypox-related research and data immediately available to the public. On July 21, 2022, the OSTP released U.S. Monkeypox Research Priorities, which outline vital outstanding research questions, objectives, and investigations.

Monkeypox Virus Genomic Epidemiology

The Africa CDC reported the initial human infection caused by the monkeypox virus was identified in Basankusu Territory, the Democratic Republic of the Congo, in 1970. On August 6, 2022, researchers estimated that APOBEC3-type mutations accumulate during human-to-human transmission at the rate of about 9 per year, which corresponds to an evolutionary rate of 4.43 × 10-5 substitutions per site per year (3.72 – 5.15 × 10-5) for a genome length of 197,210 nucleotides. This rate is approximately 20-fold greater than the long-term evolutionary rate estimated for MPXV in the non-human animal reservoir. The estimate for the date of emergence of hMPXV1 in the human population is 5-Apr-2016 (95% highest posterior density intervals of 14-Jul-2015 – 18-Dec-2016).

The genome sequence of the current MPXV outbreak (isolate name MPXV_USA_2022_MA001) became publicly available with accession ON563414 in GenBank on May 26, 2022. Then, the U.S. CDC reported on June 3, 2022, that the genetic sequencing data indicates at least two distinct MPX outbreaks are underway outside of Africa. Separately, the Nextstrain team updated the genomic epidemiology of the human MPVX on June 4, 2022, indicating at least two distinct MPXV outbreaks. The A.2 strain, which was detected in the USA in 2021, and the current outbreak is being driven by the B.1 strain of MPXV.

The Indian Council of Medical Research-National Institute of Virology disclosed on August 7, 2022, that phylogenetic analysis revealed that two cases were infected with monkeypox virus strain A.2 which belong to hMPXV-1A lineage of clade 3 (West African clade). In India, the National Institute of Virology Pune (ICMR) confirmed the West African cade in local patients on July 26, 2022. @vinodscaria with IGIBsocial Tweeted on July 27, 2022: Kerala MPX genomes in India belong to A.2, in contrast to the majority of the genomes across the world, which belongs to the B.1 lineage. Therefore, the MPXV cases in India are not linked to the European superspreader events in May 2022. Updated analysis on August 7, 2022.

Notably, the 2022 MPXV diverges from the related 2018–2019 viruses by a mean of 50 single-nucleotide polymorphisms (SNPs), which is far more (roughly 6–12-fold more) than one would expect considering previous estimates of the substitution rate for Orthopoxviruses (1–2 substitutions per genome per year). Such a divergent branch might represent accelerated evolution. 

In 2003, forty-seven confirmed and probable MPX cases were reported from Illinois, Indiana, Kansas, Missouri, Ohio, and Wisconsin. These were the first human MPX cases reported outside of Africa. All infected people became ill after contact with pet prairie dogs. Assumption: The dogs were infected after being housed near imported small mammals from Ghana and imported to Texas in April 2003.

Monkeypox Virus Wastewater Detection

The Oceanside Water Pollution Control Plant (CA 94132) wastewater samples taken in late June 2022 "showed small concentrations of viral DNA for the monkeypox disease," on July 1, 2022, 'We don't have a sense of how much disease there is, whether it's spreading, how long it might have been present before we started looking for clinical cases. But wastewater may hold clues.'

Monkeypox Clinical Research

August 16, 2022 - The U.S. CDC published Volume 28, Number 10—October 2022: Research Letter - Human Monkeypox without Viral Prodrome or Sexual Exposure, California, USA, 2022. Abstract: We report human monkeypox in a man who returned to the United States from the United Kingdom and reported no sexual contact. He had vesicular and pustular skin lesions but no anogenital involvement. The potential modes of transmission may have implications for the risk of spread and for epidemic control.

August 16, 2022 - The Annals of Internal Medicine published: Detection of Monkeypox Virus in Anorectal Swabs From Asymptomatic in a Sexually Transmitted Infection Screening Program in Paris, France. Summary: the practice of ring postexposure vaccination around symptomatic persons with probable or confirmed MPXV infection may not be sufficient to contain the virus spread. 

August 12, 2022 - The peer-review journal Nature Medicine published: Retrospective detection of asymptomatic monkeypox virus infections in Belgium. These findings show that certain cases of monkeypox remain undiagnosed and suggest that testing and quarantining of individuals reporting symptoms may not suffice to contain the outbreak.

August 12, 2022 - The UKHSA published research and analysis - Investigation into monkeypox outbreak in England: technical briefing #5.

August 10, 2022 - The Lancet published the first documented genomic sequencing case of human-to-dog (greyhound) monkeypox transmission in France.

August 6, 2022 - The Hindu published a study that revealed that the rate of genetic changes in the monkeypox virus was higher than expected and varies by country.

August 5, 2022 - The U.S. CDC Early-Release MMWR: Interim Guidance for Prevention and Treatment of Monkeypox in Persons with HIV Infection — United States, August 2022. The CDC developed clinical considerations for the prevention and treatment of MPX in persons with HIV infection, including pre-exposure and postexposure prophylaxis with JYNNEOS vaccine, treatment with tecovirimat, and infection control.

August 5, 2022 - The U.S. CDC published: Epidemiologic and Clinical Characteristics of Monkeypox Cases — United States, May 17–July 22, 2022. These data can guide clinical considerations for evaluating persons for monkeypox. Typically, monkeypox begins with a febrile prodrome, which might include malaise, chills, headache, or lymphadenopathy, followed by a disseminated rash that often includes the palms and soles. Although 42% of persons did not report prodromal symptoms, and 37% did not report fever by the time of the interview. Genital rash, although reported in fewer than 50% of cases, was common; 36% of persons developed rash in four or more body regions. 

August 2, 2022 - The Lancet published: Monkeypox virus isolation from a semen sample collected in the early phase of infection in a patient with prolonged seminal viral shedding. In our opinion, the case discussed herein supports that transmission of the monkeypox virus during sexual activity might be a viable and recognized route.

July 28, 2022 - The BMJ published Research: Clinical features and novel presentations of human monkeypox in a central London center during the 2022 outbreak: descriptive case series. A variable temporal association was observed between mucocutaneous and systemic features, suggesting a new clinical course to the disease. New clinical presentations of monkeypox infection were identified, including rectal pain and penile oedema.

July 25, 2022 - This UKHSA guidance describes case definitions to inform testing and reporting suspected monkeypox cases.

July 23, 2022 - MIT Tech Review reported: that Stanford's Sewer Coronavirus Alert Network added monkeypox to the suite of viruses it checks wastewater for. Monkeypox has been detected in 10 of the 11 sewer systems that SCAN tests, including those in Sacramento, Palo Alto, and several other cities in California's Bay Area. On July 22, 2022, SFDPH reported the total number of MPX cases in San Francisco residents to 197.

July 22, 2022 - The UKHSA published: Research and analysis - Investigation into monkeypox outbreak in England: technical briefing #4.

July 21, 2022 - The NEJm published an ORIGINAL ARTICLE: Monkeypox Virus Infection in Humans across 16 Countries — April–June 2022. In this case series, monkeypox manifested with various dermatologic and systemic clinical findings. 

July 21, 2022 - Euroserveilance published a Rapid communication - Paediatric monkeypox patient with an unknown infection source in the Netherlands in late June 2022. We were not able to identify any possible source of the infection. Whole genome sequencing positioned the patient's sequence within the clade three lineages B.1 but did not directly link to any other strains from the Amsterdam region.

July 14, 2022 - Eurosurveillance published: Frequent detection of monkeypox virus DNA in saliva, semen, and other clinical samples from 12 patients, Barcelona, Spain, May to June 2022. 'Here, we find that MPX DNA was detected in saliva at some point in all 12 patients studied, in the samples collected between 4–16 days after the onset of symptoms. With the low Cq values observed in our study in a variety of samples such as saliva, rectal swab, semen, urine, and fecal samples, further research on the infectious potential of these bodily fluids and their potential role in disease transmission by close physical contact during sexual activity is warranted.'

July 8, 2022 - The UKHSA published Technical Briefing #3. There have been four female cases and one child (under 16) in England. And the UKHSA monkeypox nowcasting model implies positive growth between 3.8% to 6.7% per day, corresponding to a doubling time of 15 days (90% CI: 10 days, 18 days).

July 8, 2022 - The ECDC's updated rapid risk assessment includes novel insights from a stochastic mathematical model developed collaboratively with the European Health Emergency Preparedness and Response Authority to assess vaccination strategies as outbreak response measures. Higher effectiveness of contact tracing can be achieved and combined with high vaccine uptake levels of 80% (upper bound estimate), the chance of MPXV outbreak control by week 12 can be maximized, with PrEP vaccination being the most effective strategy.

July 5, 2022 - The U.K. Health Security Agency stated the current outbreak clade of monkeypox is no longer classified as a high consequence infectious disease, following review by the Advisory Committee on Dangerous Pathogens (ACDP) and agreement by the U.K. four nations' public health agencies.

July 5, 2022 - A non-peer-reviewed article - Asymptomatic monkeypox virus infections among males in Belgium - concluded: 'The existence of asymptomatic monkeypox infection indicates that the virus might be transmitted to close contacts in the absence of symptoms.'

July 1, 2022 - The Lancet published: Demographic and clinical characteristics of confirmed human MPXV cases in individuals attending a sexual health center in London, UK: an observational analysis. Interpretation - Autochthonous community MPXV transmission is currently observed among MSM in London. We found a high proportion of concomitant STIs and frequent anogenital symptoms, suggesting transmissibility through local inoculation during close skin-to-skin or mucosal contact during sexual activity. Only five patients required hospitalization, and no one died. 

June 29, 2022 - The U.S. CDC's Clinical Outreach and Communication Activity presentation highlighted various technical aspects of the evolving MPXV outbreak.

June 27, 2022 - The Lancet Public Health published a Commentary from the Royal College of Obstetricians and Gynaecologists staff: Monkeypox vaccines in pregnancy: lessons must be learned from COVID-19. Data on monkeypox infection in pregnancy are minimal. However, the related orthopoxvirus, smallpox, is associated with an increased risk of maternal and perinatal morbidity and mortality, including fetal death, preterm birth, and miscarriage. Currently, no vaccine against monkeypox is approved for use in pregnancy. Whether the MVA-BN vaccine passes into breastmilk remains unknown, but this is unlikely because the vaccine virus does not replicate effectively in humans.

June 24, 2022 - The UKHSA published Technical Briefing #2 - an Investigation into the monkeypox outbreak in England (London). The MPXV strain in the U.K. contains 48 single mutations in its genome relative to 2018. Twenty-seven of these mutations are silent, and twenty-one cause changes in viral proteins.

June 24, 2022 - Researchers from Portugal's National Institute of Health in Lisbon published a study in the peer-review journal Nature showing that this MPXV belongs to clade three and that the outbreak most likely has a single origin. Although 2022 MPXV (lineage B.1) clustered with 2018–2019 cases linked to an endemic country, it segregates in a divergent phylogenetic branch, likely reflecting continuous accelerated evolution. 

June 24, 2022 - A genetic analysis published in the peer-review journal Nature Medicine revealed that the virus microevolution responsible for the monkeypox outbreak in 2022 might be related to viruses responsible for human cases in the U.K., Israel, and Singapore in 2018 and 2019.

June 23, 2022 - The Lancet published a modeling study: Projected burden and duration of the 2022 Monkeypox outbreaks in non-endemic countries. 'In conclusion, our findings align with WHO's assessment that the overall public health risk at a global level is moderate. Observed outbreaks in non-endemic countries should be contained quite quickly, particularly when adequate mitigation measures are implemented. The two intervention scenarios showed that interventions targeting contacts of primary cases could reduce the median duration of monkeypox outbreaks by between 60·9% and 75·7%.

June 13, 2022 - NIAID scientists are researching to understand monkeypox transmission and disease better. In addition, NIAID performs genomic sequencing to understand better the monkeypox virus and its strains, as well as ecological studies to understand spillover events.

June 9, 2022 - The Lancet published an Editorial:  Monkeypox: a neglected old foe. African populations have coexisted with the MPXV for decades, and it is time for research to address the needs of endemic countries. A study on the impact of smallpox vaccination on monkeypox cases among healthcare workers is ongoing in DRCongo. Another study will monitor expanded access to tecovirimat (TPOXX), the only antiviral drug licensed to treat monkeypox in the Central African Republic.

May 24, 2022 - The peer-review journal The Lancet Infectious Disease published: Clinical features and management of human monkeypox: a retrospective observational study in the U.K. Interpretation - Human monkeypox poses unique challenges, even to well-resourced healthcare systems. Prolonged upper respiratory tract viral DNA shedding after skin lesion resolution challenged current infection prevention (Jynneos) and control guidance (TPOXX).

November 14, 2019 - The peer-review journal NEJM published an Original Article in that researchers found that 14 days after a single MVA vaccination, the levels of antibodies that neutralize the monkeypox peaked at a level similar to ACAM2000. Given that the vaccines are presumed to work postexposure if given within two weeks of virus contact, this finding suggests a single dose of MVA could prevent many MPX cases. CONCLUSIONS: No safety concerns associated with the MVA vaccine were identified. Immune responses and attenuation of the primary cutaneous reaction suggest that this MVA vaccine protects against variola infection. 

September 4, 2018 - The peer-review journal Frontier in Public Health published: Emergence of Monkeypox as the Most Important Orthopoxvirus Infection in Humans. The frequency and geographical spread of human monkeypox cases have increased in recent years, and there are considerable gaps in our understanding of the disease's emergence, epidemiology, and ecology. As a result, the monkeypox virus, considered a high-threat pathogen, is causing a disease of public health importance.

June 21, 2016 - PLOS One published: A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial Investigating the Safety and Immunogenicity of Modified Vaccinia Ankara Smallpox Vaccine (MVA-BN®) in 56-80-Year-Old Subjects. The results suggest that a single dose of MVA in a 56–80 years old population was well tolerated and sufficient to rapidly boost the long-term B cell memory response induced by a prior vaccination with a traditional smallpox vaccine.

May 5, 2015 - Open Forum Infectious Disease published: Safety and Immunogenicity of Modified Vaccinia Ankara-Bavarian Nordic Smallpox Vaccine in Vaccinia-Naive and Experienced Human Immunodeficiency Virus-Infected Individuals: An Open-Label, Controlled Clinical Phase II Trial. Conclusions - MVA was safe and immunogenic in subjects infected with HIV and represents a promising smallpox vaccine candidate for use in immunocompromised populations.

March 20, 2015 - PLOS One published a Research Article: A Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox and Influenza Vaccination. Conclusions - Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. In addition, evidence of subclinical transient cardiac muscle injury post-vaccinia immunization is a finding that requires further study to include long-term outcomes surveillance.

January 17, 2014 - U.S. CDC: Volume 20, Number 2—February 2014 - Research: Genomic Variability of Monkeypox Virus among Humans, the Democratic Republic of the Congo.

March 12, 2013 - The Journal of Infectious Diseases published: Safety and immunogenicity of modified vaccinia Ankara in hematopoietic stem cell transplant recipients: a randomized, controlled clinical trial. Conclusions - MVA-BN is safe, well-tolerated, and immunogenic in HSCT recipients. These data support the use of 108 TCID50 of MVA-BN in this population.

August 30, 2010 - PNAS published: Major increase in human monkeypox incidence 30 years after smallpox vaccination campaigns cease in the DRCongo. A comparison of active surveillance data in the same health zone from the 1980s (0.72 per 10,000) and 2006–07 (14.42 per 10,000) suggests a 20-fold increase in human monkeypox incidence. Thirty years after mass smallpox vaccination campaigns ceased, human monkeypox incidence has dramatically increased in rural DRC. 

May 22, 2008 - PNAS published a peer-reviewed study using two challenge doses of MPXV administered intravenously with one dose of Dryvax (ACAM2000) manufactured by Wyeth Laboratories, Inc. Researchers found that a single injection of MVA within four days of exposure induces rapid protection in the MPX model, which suggests MVA might be effective with unimmunized individuals during a smallpox outbreak.