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ACAM2000 Vaccine

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Interim guidance

ACAM2000 is licensed by the U.S. Food and Drug Administration for immunization against smallpox for people determined to be at high risk for smallpox infection. It has been made available for the prevention of monkeypox under an Expanded Access Investigational New Drug application (EA-IND).

CDC recommends that vaccination with ACAM2000 can be considered for people aged 1 year and older who have been determined to be at high risk for infection to prevent monkeypox.

Vaccination Schedule

ACAM2000 vaccine is licensed as a single dose.

Adverse events following ACAM2000, including autoinoculation myopericarditis/pericarditis and vaccinia virus transmission to household contacts, can be serious. ACAM2000 will be made available for individuals who decide in consultation with their healthcare provider that the potential benefits of vaccination outweigh any potential risks from ACAM2000 adverse events.

Table 4. Vaccination Schedule for ACAM2000 Vaccine

ACAM2000 regimen

ACAM2000 regimen

ACAM2000 regimen

Route of administration

Route of administration

Route of administration

Injection Volume

Injection Volume

Injection Volume

Recommended number of doses

Recommended number of doses

Recommended number of doses

People age ≥1 years

ACAM2000 regimen

People age ≥1 years

Percutaneous, delivered using a bifurcated needle

Route of administration

Percutaneous, delivered using a bifurcated needle

0.0025 mL droplet of reconstituted vaccine

Injection Volume

0.0025 mL droplet of reconstituted vaccine

1 (single dose)

Recommended number of doses

1 (single dose)

Duration of Immunity

Peak immunity is expected to be reached 4 weeks after the dose of ACAM2000 is administered. The duration of immunity is unknown; however, longstanding ACIP guidance includes a recommendation for revaccination of laboratory and health care personnel designated to be at risk for ongoing occupational exposure to monkeypox virus and replication-competent vaccinia virus with a booster dose every 3 years or at least every 10 years, respectively. (Petersen et al, MMWR 2016; 65(10):257-62).

Evidence Quality

Effectiveness of ACAM2000 against monkeypox is unknown, but it is suggested by at least one study that reported that its precursor, the first-generation smallpox vaccine Dryvax, demonstrated protection against monkeypox among 1555 vaccinated contacts of 338 patients in the Democratic Republic of the Congo (then known as Zaire) (Jezek Z et al, Bulletin of the World Health Organization, 1988; 66(4):465-70  [913 KB, 6 pages]). The evidence is moderate for immunogenicity (Petersen et al, MMWR 2016; 65(10):257-62). No immune correlate of protection (i.e., minimum threshold level of antibodies needed to prevent symptoms) has been established, and clinical efficacy of ACAM2000 against monkeypox is unknown.

Safety and effectiveness of ACAM2000 in preventing smallpox or monkeypox disease have not been established in people under age 16 years. No data are available on acceptability, cost-effectiveness, feasibility, values or health equity. Regarding prevention of monkeypox disease, the level of certainty for the evidence of public health benefits is low, and desirable consequences may or may not outweigh undesirable consequences. The benefits and risks are closely balanced or uncertain but favors intervention in the context of the current public health emergency. These interim clinical considerations may change as additional evidence is considered.

Administration

Percutaneous

ACAM2000 is administered using a two-pronged (bifurcated) needle to prick the skin several times with a droplet of vaccine. ACAM2000 should not be injected by the intradermal, subcutaneous, intramuscular, or intravenous route (ACAM2000 package insert [873 KB, 11 pages]). Following a successful inoculation, virus will grow at the injection site, causing a localized infection (known as a “take”) to develop at the site of the vaccination. The lesion at the vaccination site normally develops from a red, itchy sore spot into a blister, which then dries to a scab that dries up and falls off, leaving a scar. This process can last several weeks. Providers should be properly trained on administration of ACAM2000 using a bifurcated needle and should follow up with the patient to assess the vaccination site for a vaccination “take.” Any licensed provider can administer ACAM2000; training is available online through a CDC training video.

Coadministration of ACAM2000 vaccine with other vaccines

If possible, consider delaying other vaccines when administering ACAM2000, due to the reactogenicity profile of ACAM2000. When deciding whether to co-administer other vaccine(s) with ACAM2000, the reactogenicity of ACAM2000 must be considered in balancing the benefits and risks of multiple vaccine doses administered at the same time. To prevent potential confusion around vaccine-associated rash, ACAM2000 and live injectable vaccines should not be administered on the same day. Live vaccines and ACAM2000 should be separated by at least 28 days. Health-care workers scheduled to receive an annual tuberculin skin test (TST) for tuberculosis screening should not receive the skin test until >1 month after ACAM2000 vaccination.

There are additional considerations if administering a COVID-19 vaccine. More information is available at Interim Clinical Considerations for Use of COVID-19 Vaccines.

  • Those who previously received COVID-19 vaccination (i.e. Moderna, Novavax, or Pfizer-BioNTech) previously may be given orthopoxvirus vaccine (either JYNNEOS or ACAM2000) without a minimum interval between vaccinations.
  • Those who previously received orthopoxvirus vaccination (either JYNNEOS or ACAM2000), particularly adolescent or young adult males, are recommended to consider waiting 4 weeks before receiving a COVID-19 vaccine (i.e. Moderna, Novavax, or Pfizer-BioNTech) because of the observed risk for myocarditis and pericarditis after receipt of ACAM2000 orthopoxvirus vaccine and COVID-19 vaccines (i.e. Moderna, Novavax, or Pfizer-BioNTech) and the unknown risk for myocarditis and pericarditis after JYNNEOS administration.

Best practices for multiple injections include:

  • Label each syringe with the name and the dosage (amount) of the vaccine, lot number, initials of the preparer, and exact beyond-use time, if applicable.
  • Administer each injection in a different injection site; separate injection sites by 1 inch or more, if possible.
  • Administer the ACAM2000 vaccine and vaccines that may be more likely to cause a local reaction in different limbs, if possible.

More information available at ACIP’s general best practices and Epidemiology and Prevention of Vaccine-Preventable Diseases (CDC Pink Book).

Patient counseling

Pre-vaccination counseling

Potential recipients should be informed of the risks and benefits of ACAM2000 prior to vaccination and given a copy of the FDA ACAM2000 Vaccine Medication Guide. Healthcare providers should ascertain the medical history of potential recipients to appropriately identify any contraindications to ACAM2000 vaccination. People who are eligible for and offered ACAM2000 also should be offered testing for pregnancy and HIV prior to vaccination. Recipients should also be counseled on the anticipated appearance of a normal inoculation site as well as potential side effects of vaccination and would need to sign an informed consent for ACAM2000 vaccination. Possible side effects from vaccination include pain and swelling at the inoculation site, lymphadenitis, and constitutional symptoms, such as malaise, fatigue, fever, myalgia, and headache. Self-limited skin rashes that are not associated with vaccinia virus replication in skin, including urticaria and folliculitis, may occur following vaccination.

Post-vaccination counseling

Given the limitations in knowledge about the effectiveness of vaccination in this outbreak, people who are vaccinated should continue to take steps to protect themselves from infection by avoiding close, skin-to-skin contact, including intimate contact, with someone who has monkeypox.

ACAM2000 recipients should take precautions to prevent the spread of vaccinia virus to others until the injection site lesion has completely healed (i.e., scab has fallen off to form a scar). This process can last several weeks. To avoid inadvertent inoculation with live vaccinia virus to the eyes or other anatomic sites (autoinoculation) or to other people, recipients should be advised to keep the vaccination site covered. Recipients should avoid contact (including direct skin-to-skin contact, sharing of blankets and towels, and swimming) with others who might be at risk for serious adverse events from vaccinia virus, such as people with weakened immune systems, with a history of eczema, children younger than age 12 months, or people who are pregnant.

Safety

Vaccine providers, particularly when vaccinating adolescents, should consider observing patients (with patients seated or lying down) for 15 minutes after vaccination to decrease the risk for injury should they faint. If syncope develops, patients should be observed until the symptoms resolve.

Contraindications and precautions

CDC considers the following situations to be either contraindications (not recommended) or precautions to vaccination with ACAM2000.

Table 5. Contraindications1 and Precautions for Use of ACAM2000 Vaccine

Health Condition or History or Population

Health Condition or History or Population

Health Condition or History or Population

Interim Guidance

Interim Guidance

Interim Guidance

Suggested Action(s)

Suggested Action(s)

Suggested Action(s)

History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of ACAM2000

Health Condition or History or Population

History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of ACAM2000

Contraindication

Interim Guidance

Contraindication

Do not vaccinate. Referral to an allergist-immunologist should be considered to assess the risks versus benefits of administering a dose.

Suggested Action(s)

Do not vaccinate. Referral to an allergist-immunologist should be considered to assess the risks versus benefits of administering a dose.

Three or more major cardiac risk factors (hypertension, diabetes, hypercholesterolemia, heart disease at age ≤50 years in a first-degree relative, or smoking)

Health Condition or History or Population

Three or more major cardiac risk factors (hypertension, diabetes, hypercholesterolemia, heart disease at age ≤50 years in a first-degree relative, or smoking)

Contraindication

Interim Guidance

Contraindication

Do not vaccinate.

Suggested Action(s)

Do not vaccinate.

Eye disease treated with topical steroids

Health Condition or History or Population

Eye disease treated with topical steroids

Contraindication

Interim Guidance

Contraindication

Do not vaccinate.

Suggested Action(s)

Do not vaccinate.

Congenital or acquired immune deficiency disorders, including those taking immunosuppressive medications and people living with HIV (regardless of immune status)

Health Condition or History or Population

Congenital or acquired immune deficiency disorders, including those taking immunosuppressive medications and people living with HIV (regardless of immune status)

Contraindication

Interim Guidance

Contraindication

Do not vaccinate.

Suggested Action(s)

Do not vaccinate.

Atopic dermatitis/eczema and people with a history of atopic dermatitis/eczema or other acute or exfoliative skin conditions

Health Condition or History or Population

Atopic dermatitis/eczema and people with a history of atopic dermatitis/eczema or other acute or exfoliative skin conditions

Contraindication

Interim Guidance

Contraindication

Do not vaccinate.

Suggested Action(s)

Do not vaccinate.

Pregnancy or breastfeeding

Health Condition or History or Population

Pregnancy or breastfeeding

Contraindication

Interim Guidance

Contraindication

Do not vaccinate.

Suggested Action(s)

Do not vaccinate.

Infants age <12 months

Health Condition or History or Population

Infants age <12 months

Contraindication

Interim Guidance

Contraindication

Do not vaccinate.

Suggested Action(s)

Do not vaccinate.

History of severe allergic reaction (e.g., anaphylaxis) following receipt of neomycin or polymyxin B2

Health Condition or History or Population

History of severe allergic reaction (e.g., anaphylaxis) following receipt of neomycin or polymyxin B2

Precaution

Interim Guidance

Precaution

Discuss risks and benefits with potential recipients. They may be vaccinated with a 30-minute observation period.

Alternatively, vaccination can be delayed until an allergist-immunologist is consulted, but the impact of delaying vaccination should be considered.

Suggested Action(s)

Discuss risks and benefits with potential recipients. They may be vaccinated with a 30-minute observation period.

Alternatively, vaccination can be delayed until an allergist-immunologist is consulted, but the impact of delaying vaccination should be considered.

Moderate or severe acute illness, with or without fever

Health Condition or History or Population

Moderate or severe acute illness, with or without fever

Precaution

Interim Guidance

Precaution

Consider deferring vaccination until the acute illness has improved.

Suggested Action(s)

Consider deferring vaccination until the acute illness has improved.

Children and adolescents ages 1 through 16 years

Health Condition or History or Population

Children and adolescents ages 1 through 16 years

Precaution

Interim Guidance

Precaution

Assess risks versus benefits of administering a dose; safety and effectiveness of ACAM2000 have not been established in people under age 16 years.

Suggested Action(s)

Assess risks versus benefits of administering a dose; safety and effectiveness of ACAM2000 have not been established in people under age 16 years.

1There would be no absolute contraindication to vaccination with ACAM2000 in a smallpox post-event scenario.

2 ACAM2000 vaccine contains trace amounts of neomycin and polymyxin B.

Vaccine providers should be familiar with identifying immediate-type allergic reactions, including anaphylaxis, and be competent in treating these events at the time of vaccine administration. Providers should also have a plan in place to contact emergency medical services immediately in the event of a severe acute vaccine reaction. (ACIP Adverse Reactions Guidelines for Immunization)

CDC’s Clinical Immunization Safety Assessment (CISA) Project is available to provide consultation to U.S.  healthcare providers and health departments about complex monkeypox vaccine safety questions for their patients. (Clinical Immunization Safety Assessment (CISA) Project)

Reporting of Adverse Events

The Vaccine Adverse Event Reporting System (VAERS) is the nation’s early warning system that monitors the safety of vaccines after they are authorized or licensed for use by the U.S. Food and Drug Administration. VAERS accepts and analyzes reports of adverse events following vaccination.

The vaccination provider must report all serious adverse events following administration of JYNNEOS or ACAM2000 vaccine and vaccine administration errors to VAERS.

Per the Emergency Use Authorization (JYNNEOS), the Expanded Access Investigational New Drug protocol (ACAM2000) and the HHS Monkeypox Vaccination Program Provider Agreement, the vaccination provider is responsible for mandatory reporting of the following listed events after JYNNEOS or ACAM2000 vaccination to VAERS:

  • Vaccine administration errors, whether or not associated with an adverse event
  • Serious* adverse events (irrespective of attribution to vaccination)
  • Cases of cardiac events, including myocarditis and pericarditis
  • Cases of thromboembolic events and neurovascular events

*Serious adverse events are defined as:

  • Death
  • A life-threatening adverse event
  • Inpatient hospitalization or prolongation of existing hospitalization
  • A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
  • A congenital anomaly/birth defect
  • An important medical event that based on appropriate medical judgement may jeopardize the individual and may require medical or surgical intervention to prevent one of the outcomes listed above

Providers are encouraged to also report to VAERS any additional clinically significant adverse events following vaccination, even if they are not sure if vaccination caused the event.

For information on how to submit a report to VAERS, visit VAERS – Report an Adverse Event (hhs.gov) or call 1-800-822-7967.