ACAM2000® Smallpox Mpox Vaccine Clinical Trials, Dosage, Indication, Side Effects
Emergent BioSolutions ACAM2000® is a live vaccinia virus, cell-cultured, replication-competent, single-dose vaccine that protects people against mpox and smallpox diseases. ACAM2000 is derived from plaque purification cloning from Dryvax® and calf lymph vaccine, grown in African Green Monkey kidney (Vero) cells, and tested to be free of adventitious agents. The Live attenuated vaccine does not contain variola and cannot cause mpox or smallpox. However, the ACAM2000 vaccine includes the vaccinia virus, which belongs to the poxvirus family, genus Orthopoxvirus, that can be transmitted from the vaccine recipient to unvaccinated persons with close contact with the inoculation site or exudate.
ACAM2000, a second-generation smallpox vaccine, replaced Dryvax, a first-generation vaccine derived from calf lymph. Dryvax and ACA2000 vaccines come from the New York City Board of Health strain of vaccinia. Approved by the FU.S. FDA on May 2, 2007, ACAM2000 was licensed (STN: BL 125158). The FDA approved the supplemental Biologics License Application to expand ACAM2000 indication for Mpox on August 29, 2024.
The U.S. Department of Health and Human Services awarded a contract to Emergent in September 2019 valued at approximately $2 billion over ten years for the continued supply of ACAM2000® into the U.S. Strategic National Stockpile (SNS). The approval and availability of ACAM2000 in the SNS enhance the emergency preparedness of the USA against the use of smallpox as a dangerous biological weapon, says the FDA - Military Medications Guide; (NSN): 6505-01-559-0815. On September 21, 2023, the NEJM published a Correspondence that concluded ACAM2000 vaccination prevented mpox disease in Military Personnel.
Emergent announced in August 2024 that it filed an Expression of Interest (EOI) with the World Health Organization (WHO) for the WHO's assessment of the ACAM2000® vaccine to be added as an Emergency Use Listing in connection with the May 2022 mpox outbreak. On May 27, 2022, the WHO published 'Vaccines and Immunization for mpox: Interim Guidance, as did the U.S. Centers for Disease Control and Prevention (CDC), which expanded access via Investigational New Drug Protocol, allowing the use of ACAM2000 for mpox prevention on June 30, 2022. In addition, the WHO and the CDC published updated Annexes to the Vaccines and immunization for Mpox, including ACAM2000.
Emergent BioSolutions (NYSE: EBS) is a global life sciences company based in Gaithersburg, Maryland. In 2017, Emergent acquired ACAM2000 from Sanofi Pasteur for about $125 million. Emergent BioSolutions confirmed on August 1, 2022, ACAM2000 vaccine deliveries are expected to continue under the terms of the Company's existing contract with the U.S. HHS at unit volume levels ($225-$250) consistent with 2021 deliveries.
ACAM2000 Vaccine Mpox Indication
U.S. Food and Drug Administration (FDA) approved the supplemental Biologics License Application for the expansion of the indication for ACAM2000® to include Mpox on August 29, 2024, for the prevention of mpox disease in individuals determined to be at high risk for mpox infection. In August 2024, two studies reported previous smallpox vaccination with ACAM2000 was about 70% protective against mpox clade 2. On June 23, 2023, the U.S. CDC's Advisory Committee on Immunization Practices (ACIP) published mpox outbreak and vaccine efficacy updates, and a Morbidity and Mortality Weekly Report (MMWR) presented mpox breakthrough cases in Chicago, IL. On May 18, 2023, the CDC COCA Call confirmed the Chicago Dept. of Public Health reported one man vaccinated with ACAM2000 was reinfected with Mpox. A study published on April 25, 2023, found smallpox vaccines given until the mid-1970s offer cross-reactive immunity to mpox, researchers from Karolinska Institutet reported in a study published in the scientific journal Cell Host & Microbe. Public Health France updated on March 23, 2023, confirming that previously vaccinated men were reinfected with Mpox.
ACAM2000 Vaccine Smallpox Indication
ACAM2000 is indicated for active immunization against smallpox disease for persons at high risk for smallpox infection. Smallpox vaccines are no longer routine in the U.S., although some soldiers and laboratory workers still are inoculated. ACAM2000 should not be given to people with Cardiac and Eye disease treated with topical steroids. People eligible for and offered ACAM2000 should be tested for HIV to ensure they are HIV negative, counseled on potential side effects, and signed informed consent. The U.S. FDA published Questions about Smallpox and ACAM2000. Please read this Medication Guide before you receive vaccination with ACAM2000. This Guide does not replace talking to your healthcare provider about ACAM2000 and the smallpox disease.
A study published by The Lancet in November 2022 found substantial global spatial heterogeneity in the landscape of smallpox vaccination. Vaccination coverage is estimated to range from 7% to 60% in various countries.
ACAM2000 Vaccination Health Risks
ACAM200 vaccination warnings and precautions include myocarditis, pericarditis, encephalitis, encephalomyelitis, encephalopathy, progressive vaccinia, generalized vaccinia, severe vaccinial skin infections, erythema multiforme major (including Stevens-Johnson Syndrome), eczema vaccinatum resulting in permanent sequelae or death, accidental eye infection (ocular vaccinia), which can cause ocular complications that may lead to blindness, and fetal death. These may occur following primary or revaccination with live vaccinia virus vaccines, including ACAM2000®. These risks are increased in specific individuals and may result in severe disability, permanent neurological sequelae, and/or death.
Myopericarditis following smallpox vaccination is a known health risk for military forces. The incidence of confirmed myocarditis secondary to smallpox vaccination is estimated to be 16.1 per 100,000 service members. A recent U.S. Department of Defense study estimates that Myopericarditis may impact 12 service members per 100,000. Retrospective studies confirmed with prospective studies show that >10% of patients receiving the smallpox vaccine develop new-onset dyspnoea, chest pain, or palpitations. In addition, myocarditis can range from an influenza-like illness with subtle ECG changes to acute decompensated heart failure and death.
ACAM2000 Vaccine Side Effects
As of August 2024, the FDA labeling for ACAM2000® contains a contraindication for individuals with severe immunodeficiency. Severe localized or systemic infection with vaccinia (progressive vaccinia) may occur in persons with weakened immune systems. Individuals with severe immunodeficiency who are not expected to benefit from the vaccine should not receive ACAM2000®. The risk of experiencing severe vaccination complications must be weighed against the risk of experiencing a potentially severe or fatal smallpox or mpox infection.
A study published on August 26, 2021, concluded electronic records surveillance of the entire vaccinated military population over ten years found rates of Myopericarditis, defined neurological events, and overall cardiac events consistent with those of prior passive surveillance studies involving Dryvax or ACAM2000 smallpox vaccines. The rate of adjudicated Myopericarditis among ACAM2000 recipients was 20.06/100,000 and was significantly higher for males (21.8/100,000) and for those < 40 years of age (21.1/100,000). Overall rates for cardiovascular events (Group 1 plus Group 2) were 113.5/100,000 for the ACAM2000 vaccine. The rates of subjects with one or more defined neurological events rate ratio of 1.91 (95% CI, 0.71-5.10).
Adverse events following ACAM2000 can be severe, including myopericarditis or Vaccinia virus transmission to household contacts. In addition, the side effects of the ACAM2000 vaccine smallpox vaccine were discussed in a 2010 publication. Therefore, the vaccination site requires special care to prevent the virus from spreading - Updated Medication Guide. Once vaccinated, the virus stays on the skin's surface for about 30 days and/or until the vaccine site has healed. This means other people can contract the vaccinia virus and get infected. The vaccinia virus is NOT spread by coughing, sneezing, or sexual contact.
ACAM2000 Vaccine Ingredients
ACAM2000, developed by Acambis, is a second-generation lyophilized preparation of purified virus (grown in Vero cell line) in HEPES (hydroxyethyl piperazine ethanesulfonic acid)-buffered saline, pH 7.4, containing 1% to 4% human serum albumin USP, 5% mannitol, and trace amounts of antibiotics (100 U/mL polymyxin B and 100 µg/mL neomycin) (John Becher, RPh, CDC, personal communication, 2006). It must be reconstituted before the addition of a diluent.
ACAM2000 Vaccine Dosage
ACAM2000 is administered as a single dose live virus preparation by the percutaneous route using the multiple punctures technique. ACAM2000 is administered differently than the typical "shot" associated with most vaccinations. A two-pronged stainless steel (or bifurcated) needle is dipped into the vaccine solution, and the skin is pricked several times in the upper arm with a droplet of the vaccine. The virus grows at the injection site, causing a localized infection or "pock" to form. A red, itchy, sore spot at the vaccination site within 3-4 days indicates the vaccination was successful; that is, there is "a take." A blister develops at the vaccination site and then dries up, forming a scab that falls off in the third week, leaving a small scar. The vaccine stimulates a person's immune system to develop antibodies and cells in the blood and elsewhere that can help the body fight off an actual smallpox infection if exposure to smallpox ever occurs. Therefore, individuals who receive vaccination with ACAM2000 must take precautions to prevent the spread of the vaccine virus.
ACAM2000 is provided as a lyophilized preparation of purified live virus. After reconstitution, each vial of ACAM2000 vaccine contains approximately 100 doses (0.0025 mL/dose). The concentration of vaccinia virus is 1.0-5.0 x 108 plaque-forming units (PFU)/mL or 2.5-12.5 x 105 PFU/dose determined by plaque assay in Vero cells. In addition, the product contains 2% albumin USP and trace amounts of neomycin sulfate and polymyxin B sulfate.
ACAM2000 Vaccine Breast Milk
Breastfeeding is a contraindication for smallpox vaccination. The U.S. CDC recommends against breastfeeding in women until the ACAM2000 vaccine exposure risks are evaluated. The CDC suggests temporarily withholding breastfeeding in the ten days following vaccination, during which the vaccine content is detectable in Breast Milk.
ACAM2000 Vaccine U.S. Government
On November 6, 2024, company revenues from Smallpox Medical Countermeasures (MCM) products increased $108.0 million, or 437%, during Q3 2024, compared to Q3 2023. The increase was primarily due to the timing of USG purchases of ACAM2000® and VIGIV. On September 26, 2024, Emergent announced it had secured approximately $400 million in orders in 2024 and 2025 associated with its vaccinia product portfolio, ACAM2000® and CNJ-016®. On May 30, 2023, Emergent BioSolutions announced a contract option has been secured to deliver ACAM2000® into the SNS. The option is the third of nine annual contract term extension options. It is valued at approximately $120 million and was awarded for a smaller volume than in prior years under a bilateral modification of the 10-year, roughly $2 billion contract Emergent signed with the Office of the Assistant Secretary for Preparedness and Response (ASPR) in the U.S. Department of Health and Human Services in 2019. The Army Smallpox Vaccinations Program offers insights regarding Package Insert, Medication Guides, DHA Trifold Brochure, Household contact info, and questions and answers.
ACAM2000 Vaccine CPT Codes
The AMA-issued CPT code (90622) describes the ACAM2000 vaccine manufactured by Sanofi Pastuer Biologics Co. for active immunization against smallpox disease for persons at high risk for smallpox infection.
ACAM2000 Vaccine News
August 29, 2024 - "The FDA approval of ACAM2000® for immunization against mpox in high-risk individuals further strengthens and broadens our industry-leading smallpox portfolio, which includes VIGIV® and TEMBEXA®, said Joe Papa, president and CEO of Emergent.
August 19, 2024 - 50,000 doses of ACAM2000® will be donated to Direct Relief for potential deployment in Africa.
May 30, 2023 - "This option represents the importance the U.S. government places in preparing for the threat of smallpox," said Paul Williams, SVP and Products Business Head, Emergent BioSolutions. "It also highlights the value placed by the U.S. government in maintaining domestic manufacturing capabilities and the important role of public-private partnerships in addressing known and unknown public health threats."
September 14, 2022 - The U.S. CDC Research Letter - Volume 28, Number 11—November 2022: Mpox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak. 'We report a case of Mpox in the United States in a patient vaccinated with the ACAM2000 smallpox vaccine eight years earlier. Despite his vaccination status, he still contracted the disease. In addition, he showed prodromal symptoms preceding the development of painless penile lesions that later merged.'
June 30, 2022 - The U.S. CDC published 'Considerations for Mpox Vaccination: What You Need to Know.
September 3, 2019 - Emergent BioSolutions Awarded 10-Year HHS Contract to Deliver ACAM2000 Into the Strategic National Stockpile. Robert G. Kramer Sr., president and chief executive officer of Emergent BioSolutions, stated, "Emergent applauds the U.S. government's continued focus on national security demonstrated through its long-term stockpiling strategy, which ensures a sustainable supply of critical medical countermeasures such as ACAM2000 vaccine, and its investment in a stable domestic manufacturing infrastructure to help protect the U.S. population against smallpox in the event of an attack."
June 21, 2019 - Emergent BioSolutions completes acquisition of ACAM2000® Business from Sanofi.
August 24, 2015 - U.S. FDA Risk Evaluation and Mitigation Strategy Release Letter - ACAM2000 - BLA 125158/58.
March 20, 2015 - PLOS One published - A peer-reviewed Prospective Study of the Incidence of Myocarditis/Pericarditis and New Onset Cardiac Symptoms following Smallpox Vaccination. Conclusions - Passive surveillance significantly underestimates the true incidence of myocarditis/pericarditis after smallpox immunization. Evidence of subclinical transient cardiac muscle injury post-vaccinia immunization - rate is 60 times higher than the incidence rate of overt clinical cases - requires further study to include long-term outcomes surveillance.
July 9, 2013 - Unintentional transfer of vaccinia virus associated with smallpox vaccines: ACAM2000 compared with Dryvax.
May 25, 20110 - ACAM2000™: The new smallpox vaccine for the United States Strategic National Stockpile.
April 17, 2008 - ACAM20 is0: a newly licensed cell culture-based live vaccinia smallpox vaccineStudieses with ACAM2000 indicate that it closely matches the safety of Dryvax in both non-clinical and clinical trials. ACAM2000 met two of the four primary surrogate efficacy endpoint criteria for the Phase III clinical trials. Concern over the incidence of Myopericarditis with ACAM2000 and Dryvax exists. However, so far, the cardiac events seem to be self-limited.
ACAM2000 Clinical Trials
ACAM2000 Smallpox vaccine has been involved in various clinical trials.
