ACAM2000® Smallpox Vaccine 2023
Emergent BioSolutions ACAM2000® is a live vaccinia virus, a replication-competent vaccine, to protect against smallpox disease. The Live attenuated vaccine does not contain variola and cannot cause smallpox. However, the ACAM2000 smallpox vaccine includes the vaccinia virus, which belongs to the poxvirus family, genus Orthopoxvirus.
First-generation smallpox vaccines were derived from calf lymph and included Dryvax. Second-generation vaccines are cell-cultured and include ACAM2000. Both Dryvax and ACA2000, smallpox vaccines, come from the New York City Board of Health strain of vaccinia. The Emergent's replication-competent smallpox vaccine consists of a live, infectious vaccinia virus that can be transmitted from the vaccine recipient to unvaccinated persons with close contact with the inoculation site or exudate. The vaccinia virus may cause rash, fever, and head and body aches.
ACAM2000 is approved for active immunization against smallpox disease for persons at high risk for smallpox infection. ACAM2000 is licensed in the U.S. by the Food and Drug Administration (FDA) (STN: BL 125158), and it was developed under a contract with the U.S. Centers for Disease Control and Prevention (CDC), which expanded access via Investigational New Drug protocol allows the use of ACAM2000 for mpox. Once vaccinated, the virus stays on the skin's surface for about 30 days and/or until the vaccine site has healed. Then, it can spread by touch. This means other people can contract the vaccinia virus and get infected. The vaccinia virus is NOT spread by coughing, sneezing, or sexual contact.
Approved by the U.S. FDA on May 2, 2007, ACAM2000 Smallpox Vaccine is derived from plaque purification cloning from Dryvax®, calf lymph vaccine, and grown in African Green Monkey kidney (Vero) cells and tested to be free of adventitious agents. ACAM2000 replaced Dryvax for smallpox vaccinations in February 2008. 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 this second-generation smallpox vaccine in the SNS enhance the emergency preparedness of the USA against the use of smallpox as a dangerous biological weapon, says the FDA.
On May 27, 2022, the WHO confirmed it does not endorse the ACAM2000 vaccine for mpox protection. The WHO published 'Vaccines and Immunization for mpox: Interim Guidance on June 14, 2022, as did the CDC on June 30, 2022. In addition, the WHO published updated Annexes to the Vaccines and immunization for monkeypox, including ACAM2000, interim guidance, on November 16, 2022.
The first-generation vaccine Dryvax, manufactured by Wyeth Laboratories, Inc., came from the New York City Board of Health strain of vaccinia. Dryvax was first licensed by the U.S. FDA in 1931. Military Medications Guide; (NSN): 6505-01-559-0815.
Gaithersburg, Maryland-based Emergent BioSolutions (NYSE: EBS) is a global life sciences company whose mission is to protect and enhance life. Emergent acquired ACAM2000 from Sanofi Pasteur for about $125 million cash in 2017.
ACAM2000 USA
U.S. states and territories may request access to ACAM2000 during the monkeypox outbreak from the CDC. On June 28, 2022, the U.S. government announced that ACAM2000 is believed to confer protection against monkeypox and is available under expanded access investigational new drug protocol sponsored by the U.S. CDC for vaccinating individuals at risk of monkeypox infection. However, ACAM2000 carries a greater risk of severe side effects than JYNNEOS and cannot be provided to individuals who are immunocompromised or have heart disease.
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.
The CDC stated it would work with state, territorial, and local health departments requesting the ACAM2000 vaccine to ensure that individuals are fully informed of the benefits and risks before receiving it. Policy and Management Questions and Answers.
ACAM2000 Mpox Efficacy
On May 18, 2023, the U.S. 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 Smallpox Vaccinations
A study published by The Lancet in November 2022 found substantial global spatial heterogeneity in the landscape of smallpox vaccination, with vaccination coverage estimated to range from 7% to 60% within admin-1 regions (i.e., regions one administrative level below country) globally, with little uncertainty (99·6% of regions have an SD less than 5%).
ACAM2000 Myopericarditis Risk
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 Department of Defense study estimates 12 per 100,000 in a review of 730,000 service members.
ACAM2000 Indication
ACAM2000 is indicated for active immunization against smallpox disease for persons at high risk for smallpox infection. Smallpox vaccines are no longer routine, 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.
ACAM2000 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 use by the addition of a diluent.
ACAM2000 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. 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 Side Effects
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 serious, including myopericarditis or Vaccinia virus transmission to household contacts. In addition, ACAM2000 vaccine smallpox vaccine side effects were discussed in a 2010 publication. Therefore, the vaccination site requires special care to prevent the virus from spreading - Updated Medication Guide.
ACAM2000 Heart Health Risk
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 Military Use Considerations
The Army Smallpox Vaccinations Program offers insights regarding Package Insert, Medication Guide, DHA Trifold Brochure, Household Contacts Info, and questions and answers.
ACAM2000 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 Revenues 2022
On August 1, 2022, Emergent disclosed its ACAM200 revenue forecast was $225-$250 million. Previously, the Company reported $14.4 million in ACAM2000 sales for the vaccine in the first quarter of 2022. On January 9, 2022, the Company announced that ACAM2000 vaccine deliveries are expected to continue under the existing contract with the U.S. HHS at unit volume levels consistent with 2021 deliveries. On November 4, 2021, the Company reported ACAM2000 product revenues were $80.7m compared to $1m in 2020.
ACAM2000 News For 2008 - 2022
September 14, 2022 - The U.S. CDC Research Letter - Volume 28, Number 11—November 2022: Monkeypox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak. 'We report a case of monkeypox in the United States in a patient who had been 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.'
September 2, 2022 - Medscape published an Editorial: How effective is the smallpox vaccine against monkeypox, and how was it identified as potentially protective against monkeypox?
August 13, 2022 - CNN reported the U.S. FDA detailed options the agency had considered. But the use of alternative vaccines to prevent monkeypox "was determined to be either impractical or inadvisable at this time," according to the letter. Specifically, the ACAM2000 vaccine, which is FDA-approved for preventing smallpox, "may not be appropriate now for a potentially immunocompromised population," the letter said.
August 5, 2022 - Newsweek reported Dr. Fauci explained why the U.S. isn't using the ACAM2000 vaccine to combat monkeypox.
August 4, 2022 - The California Department of Public Health confirmed to KRON4 that it had ordered 200 doses of the ACAM2000 vaccine.
June 30, 2022 - The U.S. CDC published 'Considerations for Monkeypox Vaccination; What You Need to Know.
June 28, 2022 - The Biden-Harris Administration announced it provides vaccines to protect high-risk groups across the USA. The new U.S. vaccine strategy will address the spread of the monkeypox virus by giving vaccines to individuals at high risk and mitigating the spread of the disease.
June 17, 2022 - The U.S. CDC confirmed the 113th monkeypox case reported in twenty states.
May 23, 2022 - CNN reported Dr. Jennifer McQuiston with the U.S. CDC stated during a briefing today: 'ACAM2000, that could be used to prevent monkeypox, she said, and the 'U.S. stockpile' has more than 100 million doses.'
May 20, 2022 - The U.S. CDC issued an Alert - Level 2, Practice Enhanced Precautions, confirming cases of monkeypox have been reported in Europe, North America, and Australia. If you become sick and could have monkeypox, delay travel by public transportation until you have been cleared by a healthcare professional or public health officials.
April 8, 2022 - The U.S. CDC published: Monkeypox in a Traveler Returning from Nigeria — Dallas, Texas, July 2021.
February 24, 2022 - The Company confirmed ACAM2000 vaccine revenues recognized in Q4 2021 reflect delivery of doses into the U.S. SNS resulting from the July 2021 exercise of the second of nine annual contract term extension options under the Company's 10-year supply agreement with the U.S. Government. This latest option is valued at approximately $182 million.
January 13, 2022 - Emergent BioSolutions Presented At the 40th Annual J.P. Morgan Virtual Healthcare Conference.
November 18, 2021 - The U.S. CDC reported on November 15, 2021, the U.S. Government was notified of the report of a small number of intact, frozen vials labeled "smallpox" discovered by a laboratory worker while cleaning out a freezer in a facility that conducts vaccine research in Pennsylvania. The freezer facility was immediately secured, and staff followed standard protocols for notifying the CDC of such a potential discovery. The vials were securely sent to CDC for testing on November 18 to determine their contents. No one was exposed to the contents of the vials.
November 4, 2021 - During an interview with the U.K. Health Select Committee Jeremy Hunt and Bill Gates warned that governments must prepare for pandemics and smallpox terror attacks by investing billions in research and development.
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 - ACAM2000: a newly licensed cell culture-based live vaccinia smallpox vaccine. The studies 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.
