# Imvamune Vaccine
Imvamune is a live attenuated, non-replicating vaccine that is approved in Canada for protection against smallpox, mpox, and other orthopoxvirus related illness; it is 3rd generation smallpox vaccine. It is produced from the Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) strain of orthopoxvirus and was developed to provide an alternative for the vaccination of immunocompromised individuals and those with atopic dermatitis, who could not safely receive earlier generation (replicating) smallpox vaccines.
Health Canada first approved the use of this vaccine for active immunization against smallpox in a public health emergency in 2013. In 2020, Health Canada expanded approval of Imvamune to include additional indications, specifically for mpox and related orthopoxvirus infections in adults 18 years of age and older at high risk of exposure. The use of Imvamune has not been studied in individuals less than 18 years of age or in those who are pregnant or breastfeeding.
Imvamune can be used as post exposure prophylaxis (PEP) in individuals with a recent high-risk mpox exposure. This is based on evidence extrapolated from animal studies and historical experience with smallpox vaccine in humans which suggest that vaccination after an exposure to mpox infection may prevent infection or lessen disease severity in those who become infected.
Individuals with signs or symptoms of mpox infection should not receive the vaccine as the vaccine is not indicated in the treatment of mpox infection.

# Use of Imvamune in Ontario
Given the current epidemiology in Ontario, Imvamune should be offered as a two-dose primary series, with at least 28 days between first and second doses for individuals currently eligible for pre-exposure or post-exposure vaccination.
A full dose, 0.5ml of Imvamune, should be given via the subcutaneous (SC) route for each dose. This approach will continue to be evaluated with any changes in the epidemiology and evidence surrounding the vaccine.
Imvamune should be considered for the following:
- Pre-exposure vaccination -when Imvamune is administered before known exposure to the virus
- Post-exposure vaccination -when Imvamune is administered for individuals who have had a high-risk exposure to a probable or confirmed case of mpox, or within a setting where transmission is happening.
1) For the Purposes of Pre-Exposure Vaccination a) Two-spirit, non-binary, transgender cisgender, intersex, or gender-queer individuals who self-identify or have sexual partners who self-identify as belonging to the gay, bisexual, pansexual and other men who have sex with men (gbMSM) community AND at least one of the following:
- Had a confirmed sexually transmitted infection within the last year
- Have or are planning to have two or more sexual partners or are in a relationship where at least one of the partners may have other sexual partners,
- Have attended venues for sexual contact (i.e., bath houses, sex clubs) recently or may be planning to, or who work/volunteer in these settings; or
- Have had anonymous sex (e.g., using hookup apps) recently or may be planning to; and/or
- Are a sexual contact of an individual who engages in sex work.
b) Individuals who self-identify as engaging in sex work or are planning to, regardless of self-identified sex or gender.
Household and/or sexual contacts of those identified for pre-exposure vaccination eligibility in parts (a) and (b) above AND who are moderately to severely immunocompromised (see Appendix A) or pregnant may be at higher risk for severe illness from a mpox infection may be considered for pre-exposure vaccine and should contact their healthcare provider (or their local public health unit) for more information. Also see relevant sections under "Special Populations" for additional considerations.

# 2) For the Purposes of Post-Exposure Vaccination throughout Ontario
The provision of Imvamune for post-exposure vaccination requires an assessment of the risk of exposure by the public health unit. If the identified person has a risk of potential exposure that is expected to continue beyond 28 days following the first 0.5mL SC dose, a second dose , 0.5mL SC, should be offered.
The first dose should be offered ideally within 4 days (up to 14 days) from the date of the last exposure to individuals who are a high risk contact of a confirmed or probable case of mpox. The second dose should be offered at least 28 days after the first dose.
Anyone who self-identifies as a high risk contact of a confirmed or probable case of mpox should contact their local public health unit for further assessment to see if post-exposure vaccination would be recommended.
Intermediate risk contacts may also be offered post-exposure vaccination, following the public health unit's assessment of individual risks and benefits (i.e., to balance the risks from exposure, protection from vaccination and potential side effects from the vaccine).
Post-exposure vaccination is not recommended for low-risk contacts including health care workers (see Table 1). 

# Special Populations

# Individuals with History of Previous Smallpox Vaccine
Individuals eligible for Imvamune as pre-exposure vaccination or post-exposure vaccination who previously received either an older generation replicating (live) smallpox vaccine or Imvamune can be re-vaccinated:
- For individuals with a history of receiving 1 dose of a live smallpox vaccine, a single dose of Imvamune is recommended.
- For individuals who completed a 2-dose series of Imvamune more than 2 years ago, a single booster dose of Imvamune is recommended.
- For individuals who completed a 2-dose series of Imvamune within the last 2 years, no further doses are recommended.

# Individuals Who have had Previous Mpox Infection
At this time, individuals who have been diagnosed as a confirmed case of mpox in the current outbreak are NOT recommended to receive the mpox vaccine; this is based on the limited utility of the vaccine given that these persons are expected to have infection-mediated immunity due to recent infection. This recommendation is based on current evidence and may change as more information becomes available.

# Research Laboratory Employees
Research laboratory employees working directly with replicating orthopoxviruses, are eligible to receive two doses of Imvamune at least 28 days apart as postexposure vaccination or pre-exposure vaccination if there is an ongoing risk of exposure.

# Moderately to Severely Immunocompromised
Individuals who are moderately to severely immunocompromised and are currently eligible for pre-exposure vaccination should receive two doses of the Imvamune vaccine administered at the recommended interval. Please refer to:
- Appendix A for the definition of moderate to severe immunocompromise; and
- Appendix B for guidance on how to verify eligibility in this population.
Clinical trials of Imvamune have included people living with human immunodeficiency virus (HIV) with a CD4 count of equal or greater than 100. There is less experience in individuals with severe immunosuppression. Additional risk/benefit discussion is indicated for those with severe immunosuppression prior to receiving vaccine as post-exposure vaccination.

# Allergy/Hypersensitivity
- Individuals who are hypersensitive to this vaccine or to any ingredient in the formulation or component of the container should not receive the vaccine. A list of ingredients can be found in the product monograph.
- Note: Imvamune may contain trace amounts of antibiotics (gentamicin and ciprofloxacin) and egg products (egg cell DNA and protein) which are used during the vaccine production process. Individuals with known hypersensitivity to these products are still able to safely receive Imvamune but should be monitored for an additional 15 minutes (30 minutes total) after vaccine administration.

# Pregnancy and Breastfeeding
- There are very limited data on the use of Imvamune in pregnancy. No clinical trials have been conducted in pregnant individuals, although approximately 300 pregnancies have been reported to the manufacturer with no safety issues identified.
- There are no data on whether the vaccine is excreted in breastmilk, although this is unlikely as the vaccine is non-replicating.
- Additional risk/benefit discussion is indicated for those who are pregnant or breastfeeding prior to receiving vaccine as post-exposure vaccination.

# Children and Youth
- Imvamune vaccine is not authorized for use in persons under 18 years of age, and has not been studied in this age group, although it has been offered
to children as PEP in previous United Kingdom mpox incidents as cited in UK PEP guidance. Clinical trials have studied other vaccines (TB and malaria)
using Modified Vaccinia Ankara (MVA) as a vector in children with a reassuring safety profile.
- Additional risk/benefit discussion is indicated for persons under 18 years of age prior to receiving vaccine as post-exposure vaccination. For the process of setting up infectious disease consults for mpox post-exposure vaccination in pediatric populations, please refer to Appendix C.

# Persons with Atopic Dermatitis
- Persons with atopic dermatitis may have more frequent and more intense reactions after vaccination. This population was specifically studied in clinical trials as those with a history or presence of atopic dermatitis are contraindicated to receive the previous generation of smallpox vaccine (ACAM2000).

# Potential Side Effects of Imvamune
The most common side effects include reactions at the injection site like pain, erythema, induration and swelling. The most common systemic reactions observed after vaccination are fatigue, headache, myalgia, and nausea. Most of the reported adverse drug reactions observed in clinical trials were of mild to moderate intensity and resolved within the first seven days following vaccination.
Older generation (i.e., replicating) smallpox vaccines have been associated with myocarditis. No case of myocarditis or pericarditis was identified in clinical trials of Imvamune, however post market surveillance of vaccine recipients identified cardiac adverse events of special interest (AESIs) including asymptomatic troponin elevation, abnormal ECG findings, tachycardia, and palpitations. Cardiac AESIs were reported to occur in 1.4% (91/6,640) of Imvamune recipients and 0.2% (3/1,206) of placebo recipients who were smallpox vaccine-naive. Individuals should be counselled to seek medical attention if cardiac symptoms (i.e., chest pain, shortness of breath, palpitations) develop following vaccination with Imvamune.

# Informed Consent
The Health Care Consent Act, 1996 provides specific information as to the consent required for treatment. According to the HCCA, and the College of Nurses of Ontario (CNO) and College of Physicians and Surgeons of Ontario (CPSO) standards, nurses and physicians are accountable for obtaining consent when providing treatment. It is therefore the responsibility of the health practitioner who is proposing the treatment to take reasonable steps to ensure that informed consent for that treatment is obtained.
According to the HCCA, consent to treatment for a capable person is informed if, before giving the consent:
a. the person received the information about the treatment that a reasonable person in the same circumstances would require to make a decision; and b. the person received responses to his/her requests for additional information about the treatment.

# This information must include:
- The nature of the treatment
- The expected benefits of the treatment
- The material risks of the treatment
- The material side effects of the treatment
- Alternative courses of action
- The likely consequences of not having the treatment.
The elements required for consent to treatment include:
- The client must have the capacity to consent
- The consent must relate to the treatment
- The consent must be informed
- The consent must be given voluntarily
- The consent must not be obtained through misrepresentation or fraud.

# Evidence of Consent:
Although the HCCA states that consent to treatment may be expressed or implied (i.e., written or verbal), the CNO and CPSO strongly advise nurses and physicians to document that consent was obtained from the client. Examples include: 1) a signed consent form and/or 2) documented consent in the client's health records.

# How to order Imvamune
To order the vaccine, the local public health unit must complete this electronic form. Please contact the Vaccine Policy & Programs Branch at vaccinesupplyandlogistics@ontario.ca for any questions.
Clinicians who think they have a patient (i.e., a contact of a case) who might be recommended to receive post-exposure vaccination using the criteria above should contact their local public health unit.

# Co-Administration of Imvamune
Interactions with Imvamune and other vaccines have not been established. If vaccine timing can be planned, it is recommended to wait at least 4 weeks for live vaccines (or COVID-19 vaccines) or 2 weeks for inactive vaccines before or after administration of Imvamune. These suggested waiting periods are precautionary but may help prevent erronerous attribution of an AEFI to one particular vaccine or the other.
However, the administration of Imvamune as pre-or post-exposure vaccination should not be delayed in an individual who has recently received another vaccine. If vaccines must be co-administered, immunization on separate limbs is recommended to minimize the risk of interaction.

# Storage Conditions
Please see mpox Virus (gov.on.ca) for information on storing and handling Imvamune. - For guidance on the timing of vaccine administration for transplant recipients and those requiring immunosuppressive therapies, a more comprehensive list of conditions leading to primary immunodeficiency, and for further information on immunosuppressive therapies, refer to Immunization of Immunocompromised Persons in the Canadian Immunization Guide (CIG), Part 3 -Vaccination of Specific Populations.

# Reporting Adverse Events Following Immunization

# Table 2. List of Significantly Immunosuppressive Medications
The table below lists many of the common immunosuppressive medications used in Ontario, but it is not an exhaustive list. If an individual is receiving an immunosuppressive biologic agent and they do not have a prescription, or their medication is not listed below, they can receive a referral form/letter indicating their eligibility due to their immunocompromised status from their health care provider to receive a second dose of the Imvamune vaccine.
Vaccine providers can refer to Appendix B for guidance on how to verify eligibility.

# Class Generic Name(s) Brand Name(s)
Steroids (>20 mg per day of prednisone or equivalent for at least 2 weeks)
- prednisone
- dexamethasone - Decadron - methylprednisolone - DepoMedrol - SoluMedrol - Medrol

# Roles and Responsibilities

# PHUs
- Proactively develop internal processes and resources as part of their local mpox response. This includes:
- Resources for staff to provide appropriate counseling to individuals identified as contacts of a known mpox case and/or their guardians about PEP with Imvamune (e.g., risks and benefits of receiving PEP).
- Identifying local pediatric specialist(s) as well as determining the threshold or indications for triggering a pediatric consult for clinical advice and/or support in vaccine administration.
- Where pediatric specialists are not available locally, PHUs should reach out to their regional tertiary pediatric hospital and consult ID (e.g., HSC).
- A process to ensure timely transportation of Imvamune if requesting an external provider (e.g., a local pediatrician) to support vaccine administration.
- Conduct exposure risk assessment of all contacts of a known/confirmed or suspected case of mpox.
- Obtain and provide the following information when consulting a pediatric specialist: o Clinical question/request (e.g., provide guidance to PHU on counseling, provide direct counseling to parents, request for vaccine administration etc.); and o Contact information for parent/guardian.

# Ministry of Health
- Provide and communicate provincial level guidance on mpox related policies to PHUs, including the establishment of an eligibility criteria for Imvamune for use of mpox PEP.

# Public Health Ontario (PHO)
- Provide technical and scientific support to PHUs on public health aspects of mpox case and contact management, including questions on:
- Exposure risk assessment o Scientific evidence for Imvamune

# Pediatric specialist(s)
- Provide guidance/support to PHU when consulted on clinical questions relating to mpox, including the administration of Imvamune, in pediatric populations.
- When requested by PHU, provide direct counseling to the contact and/or their parents/guardians about the risks and benefits of Imvamune PEP.
- When requested by PHU, support Imvamune administration in a child as indicated.

# Appendix A
Moderately to severely immunocompromised is defined as:
- Individuals receiving dialysis (hemodialysis or peritoneal dialysis)
- Individuals receiving active treatment 2 (e.g., chemotherapy, targeted therapies, immunotherapy) for solid tumour or hematologic malignancies
- Recipients of solid-organ transplant and taking immunosuppressive therapy
- Recipients of chimeric antigen receptor (CAR)-T-cell therapy or hematopoietic stem cell transplant (within 2 years of transplantation or taking immunosuppression therapy)
- Individuals with moderate to severe primary immunodeficiency (e.g., DiGeorge syndrome, Wiskott-Aldrich syndrome)
- Individuals with HIV with current CD4 count  200/mm3 or CD4 fraction  15% or detectable viral load (i.e., not suppressed)
- Individuals receiving active treatment with the following categories of immunosuppressive therapies: anti-B cell therapies 3 (monoclonal antibodies targeting CD19, CD20 and CD22), high-dose systemic corticosteroids (refer to the Canadian Immunization Guide for suggested definition of high dose steroids), alkylating agents, antimetabolites, or tumor-necrosis factor (TNF) inhibitors and other biologic agents that are significantly immunosuppressive (See Table 2).

# Class Generic Name(s) Brand Name(s)

# Class Generic Name(s) Brand Name(s)
Anti-TNF (tumor necrosis factor)

# Appendix B Clinic Guide to Verifying Immunosuppressive Prescriptions for Imvamune Eligibility
The following information is guidance for vaccination clinics administering Imvamune to individuals receiving immunosuppressive therapies who present a prescription of their medication (see Appendix A).
Step 1: Verify Prescription Details
- The individual should present a current prescription receipt from a pharmacy, or present a current medication bottle/package that includes the following information:
- Date of prescription  To be considered current, the prescription should be prescribed or refilled within the past 6 months.
 Active treatment for patients receiving B-cell depleting therapies (monoclonal antibodies targeting CD19, CD20 and CD22) includes patients who have completed treatment within 12 months.
- Patients first and last name  The first and last name should be compared to a piece of identification.
- Address and telephone number of the pharmacy
Step 2: Cross-Reference Drug Name
- Confirm that the drug name is listed in Table 2.
- Table 2 provides a list of immunosuppressive medications that qualifies individuals to receive Imvamune.
- This list may not be comprehensive. If an individual presents a prescription of a medication that is not listed in Table 2, they should be directed to their healthcare provider to receive a referral form/letter for a second dose of Imvamune
Step 3: Administer Vaccine