Vaccinia virus: Infectious substances pathogen safety data sheet 

Section I – Infectious agent

Name

Vaccinia virus

Agent type

Virus

Taxonomy

Family

Poxviridae^{Footnote 1}

Genus

Orthopoxvirus

Species

vaccinia  

Synonym or cross-reference

Orthopoxvirus vaccinia is commonly known as Vaccinia virus (VACV or VV)^{Footnote 2Footnote 3}. Historical naming conventions of diseases based on pathogenesis, animal host, and phenotypic characteristics have many vaccinia and vaccinia-like viruses grouped together; hence, Rabbitpox virus (RPXV) and Buffalopox virus (BPXV) are also assigned to the Orthopoxvirus vaccinia species and are considered sub-lineages of VACV^{Footnote 3Footnote 4}. VACV infection is also commonly referred to as the zoonotic disease it causes, bovine vaccinia (BV)^{Footnote 4}.

Characteristics

Brief description

VACV virions are generally oval or brick-shaped, 220-450 nm long x 140-260 nm wide x 140-260 nm thick, with a lipoprotein surface membrane displaying tubular or globular units, or a regular spiral filament^{Footnote 5}. The surface membrane encloses a biconcave or cylindrical core that contains the DNA genome and proteins organized in a nucleoprotein complex^{Footnote 5}. The genome of VACV consists of a linear molecule of double-stranded DNA, 191 kbp in size, with covalently closed ends and a G+C content of approximately 36%^{Footnote 5Footnote 6Footnote 7}.

Properties

The VACV genome is bidirectional, and genes are categorized as R (right) and L (left) to indicate the genomic orientation of the open-reading frames (ORFs)^{Footnote 5Footnote 6}. The central 102 kbp region of the genome encodes approximately 100 proteins involved in virus replication, morphogenesis, and dissemination, which are highly conserved among members of the genus^{Footnote 5}. In contrast, the terminal regions of the genome encode less conserved proteins involved in host immune response and provide replicative advantages in the host and are unique to individual Orthopoxvirus species^{Footnote 5}.  

Poxvirus replication occurs predominantly, if not exclusively within the cytoplasm of mammalian cells^{Footnote 5}. Virion entry occurs either by macropinocytosis and release from an endosomal compartment or by direct fusion of the viral membrane with the plasma membrane^{Footnote 5Footnote 8}.

Section II – Hazard identification

Pathogenicity and toxicity

Human infections with VACV and cowpox virus (CPXV), a related poxvirus, produce similar clinical syndromes as both produce ulcerative skin lesions that progress through a well-characterized sequence of events^{Footnote 7}. Subsequent to exposure, the site develops a papule which becomes vesicular after 3-5 days, and at days 8-10, the vesicles become pustular and lesions reach their maximum size^{Footnote 7}. At this point, lesions are reported to be painful with surrounding edema and erythema^{Footnote 7Footnote 9} . At days 14-21, the lesions dry forming a hard black crust which typically separates, consequently leaving a scar^{Footnote 7Footnote 9}. Infection is usually associated with systemic symptoms including fever, lymphadenitis, fatigue, and malaise (commonly described as influenza-like)^{Footnote 7}. Bovine vaccinia, caused by VACV, causes nodular, ulcerated, and necrotic lesions (primarily on the hands and arms), and in addition to the typical systemic symptoms of VACV infection, affected individuals may also experience anorexia and arthralgia^{Footnote 8Footnote 10Footnote 11Footnote 12}. Clinical signs and symptoms of buffalopox, caused by BPXV, resembles those of VACV in humans^{Footnote 13Footnote 14}. In humans, RPXV has been reported to present as a respiratory illness, including cough, shortness of breath, and chest tightness, along with fever^{Footnote 15}.

Historically, the most widely used virus for smallpox inoculation has been VACV which has been associated with mild to severe side effects^{Footnote 16}. Common symptoms after vaccination include fever, muscle aches, regional lymphadenopathy, fatigue, headache, nausea, rash, and soreness at the vaccination site^{Footnote 16}. Serious adverse events associated with VACV vaccination include progressive vaccinia or vaccinia necrosum (progressive spread of VACV beyond the vaccination site), eczema vaccinatum (dissemination from the vaccination site that occurs in people with atopic dermatitis), generalized vaccinia (the development of a disseminated vesicular rash following vaccination), post-vaccination encephalitis (VACV infection in the nervous system), fetal vaccinia (transmission of VACV infection to the fetus following the vaccination of the pregnant woman), and accidental infection (auto-inoculation from the initial vaccination site to another site)^{Footnote 17Footnote 18}. Safer vaccines were thus needed and recently, a non-replicating Vaccinia strain has been shown to not cause such effects and  considered to be much safer in comparison to vaccine prepared with replication-competent strains^{Footnote 19}.

In cattle, the clinical course of BV is characterized by the appearance of a maculopapular rash that progresses to papules, vesicles, pustules, and subsequently to scab lesions, which heal about 20 days after infection^{Footnote 10}. Characteristic signs of buffalopox in buffalos include a local pox exanthema (pustulation with central necrosis) and localized pox-lesions^{Footnote 13}. Severe VACV lesions on the teats and udders can lead to mastitis and other secondary infections in both cattle and buffalo^{Footnote 10}.

RPVX is primarily known to infect laboratory rabbits (Oryctolagus spp.), and is characterized by pox lesions, fever, nasal and ocular discharge, difficulty breathing, and weight loss^{Footnote 20Footnote 21}. The cutaneous lesions include skin rash, subcutaneous edema, and edema of the mouth^{Footnote 20}.

Epidemiology

VACV has been used extensively as a vaccine to prevent smallpox; however, the origin and natural history of VACV remains unclear^{Footnote 22Footnote 23}. VACV and its sub-lineages, RPXV and BPVX, have been isolated from around the globe^{Footnote 14Footnote 15Footnote 24}. BPXV is primarily observed in Asia and the Middle East and VACV in South America^{Footnote 4}. Outbreaks of BPXV have occurred in Asian buffalo (Bubalus bubalis) herds in India, Egypt, Pakistan, Nepal, Bangladesh, and Italy^{Footnote 10}.

The first documented outbreak of VACV in Brazil occurred in 1999, which marked the emergence of BV and VACV becoming endemic in the country^{Footnote 4Footnote 9Footnote 24}. Rural environments, especially dairy farms, are crucial sources of VACV transmission^{Footnote 4}. The state of Minas Gerais, Brazil, has been identified as the epicenter of BV outbreaks with a total of 97 individual case notifications of BV in humans recorded from 2001 to 2021^{Footnote 24}. Of those cases, most were of working age (84/97) and the majority of respondents reported that their exposure to VACV was directly related to occupational activities (50/66) involving direct contact with cattle. Brazilian VACV (VACV-BR) belong to at least two distinct clusters/clades, GI and GII, based on disease prevalence, host range, and genetic differences^{Footnote 4Footnote 12Footnote 25}. GI VACV-BR strains are isolated more frequently in Brazil than GII strains^{Footnote 10Footnote 12}.

In addition to Brazil, asymptomatic VACV circulation has been described in Argentina and Uruguay in cattle and in both humans and cattle in Columbia^{Footnote 10Footnote 26Footnote 27}.

The risk of serious outcomes associated with VACV infections is increased in individuals with cardiac disease (or a history of cardiac disease), active eye disease being treated with topical steroids at the time of administration, congenital or acquired immune deficiency disorders (including those taking immunosuppressive medications), active skin conditions (such as eczema and atopic dermatitis), pregnant or breastfeeding women, and infants less than 12 months of age^{Footnote 17Footnote 28}.

Host range

Natural host(s)

VACV has a broad range of hosts including humans, rodents, non-human primates, marsupials, cattle, donkeys, swine, dogs, cats, horses, and buffalo (such as Asian buffalo [Bubalus bubalis])^{Footnote 4Footnote 10Footnote 24Footnote 25Footnote 29Footnote 30}.

Other host(s)

Laboratory rabbits are the only known host for RPXV^{Footnote 20}.

Infectious dose

Unknown. When used as a vaccine the titre is 10⁸ pock-forming units per millilitre^{Footnote 16}.

Incubation period

Approximately 3 to 5 days after exposure, a VACV papule develops alongside systemic clinical signs^{Footnote 7Footnote 9}.

In cattle, the incubation of BV is described as a short incubation period, between 3 to 5 days^{Footnote 10}.  

Communicability

The vast majority of VACV infections in humans are associated with the administration of the live vaccine^{Footnote 7}. Inadvertent infection of VACV can occur due to auto-inoculation (VACV disseminates from the vaccination site to another site), to another person via direct contact, and/or indirect contact with exudate from lesions or contaminated fomites^{Footnote 17Footnote 18Footnote 28Footnote 31}. Contact with VACV-infected animals can also result in human VACV infection and vice-versa^{Footnote 32} .

Ingestion of contaminated material (such as milk from infected lactating cows), aerosol inhalation, and injection have been determined to be possible routes of transmission for VACV^{Footnote 10Footnote 15Footnote 33}.

Section III – Dissemination

Reservoir

None.

Zoonosis

VACV transmission can occur through both traditional zoonoses (animal to human transmission) and reverse zoonosis (human to animal transmission)^{Footnote 4Footnote 31Footnote 32}.

Vectors

None.

Section IV – Stability and viability

Drug susceptibility/resistance

Antivirals effective against VACV include cidofovir or a related acyclic nucleoside analogue (HPMPO-DAPy), trifluridine, and adefovir dipivoxil^{Footnote 34Footnote 35Footnote 36}. Additionally, thymidine analogues and deoxyuridine analogues such as idoxuridine and triflurodine, mycophenolate mofetil, and tranilast have shown some efficacy against VACV as well^{Footnote 35Footnote 37}.

Susceptibility to disinfectants

VACV is susceptible to bleach (sodium hydroxide) at both 1:10 and 1:4 dilutions; 0.5-2% formaldehyde; 0.1% peracetic acid; quaternary ammonium compounds such as 0.2% N-cetylpiridinium chloride, 0.0125-0.025% benzalkonium chloride, 0.015% quaternary ammonium, and solutions of 0.01% chlorohexidine gluconate with 0.025% quintenary ammonium or 0.007% glutaraldehyde with 0.01% quintenary ammonium; 0.02% glutaraldehyde; phenolic compounds such as 2% phenol and 0.12% o-phenylphenol; 40% ethanol; 30% 2-propanol; 0.02% Mercury (II) chloride; 0.1-0.25% formic acid; 1% propionic acid; 1% citric acid; 1-2% acetic acid; 0.02% potassium permanganate; 1% hydrogen peroxide; and 0.045% iodine^{Footnote 38Footnote 39Footnote 40}. In addition, VACV can be inactivated by Sanytex (a commercial disinfectant) at a concentration of 10% and 30%^{Footnote 41}.

VACV has a notable resistance to the solvent/detergent combinations of tri-n-butyl phosphate (TNBP) with Triton X-100 and TNBP with Tween 80^{Footnote 42}. To reach inactivation level of 4 log, incubation times of 10 minutes for TNBP/Triton X-100 or 6-24 hours for TNBP/Tween 80 were required.

Physical inactivation

VACV can be inactivated by dry heat at 95ºC for 2 hours^{Footnote 38}. The heat-sensitive fraction of the virus is inactivated by moist heat at 60ºC, while the heat-resistant fraction may take higher temperatures to be fully inactivated^{Footnote 38Footnote 43}. VACV in its aerosolised form is sensitive to UV light, both UVB (or solar radiation) and UVC, at 290-320 nm and 254 nm, respectively^{Footnote 38Footnote 44Footnote 45}.

Survival outside host

Poxviruses show a high environmental stability and remain contagious over a period of several months in an ambient environment^{Footnote 40}. They’re also highly resistant to drying and remain stable over a range of pH values (4.5-10).

Dried VACV has been reported to remain viable after 35 weeks being stored at 4ºC^{Footnote 40}, and for 39 weeks at 6.7% moisture and 4ºC^{Footnote 38}. Additionally, VACV shed in mouse feces has been reported to remain viable for 20 days or more at environmental temperature and humidity in Brazil, with viral DNA being detected until 60 days post-environmental exposure^{Footnote 46}.

Section V – First aid/medical

Surveillance

The definitive method of diagnosis for VACV is through molecular, serological, and morphological identification via Plaque Neutralization test (PRNT) assays, electron microscopy, polymerase-chain reaction (PCR) assays, and/or immunohistochemistry (IHC) assays^{Footnote 4Footnote 10Footnote 13Footnote 15Footnote 24Footnote 32}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook.

First aid/treatment

Depending on the severity of the illness, treatment for the VACV infection involves symptom management and supportive care which may include the administration of anti-inflammatories, anti-pyrectics, and anti-infectives^{Footnote 15Footnote 47}. Vaccinia immune globulin (VIG), a sterile and purified gamma globulin fraction of plasma taken from healthy donors previously vaccinated with VACV, can be administered for the management of serious complications associated with VACV vaccination^{Footnote 47}. VIG has also shown to reduce mortality rates of eczema vaccinatum and resolve progressive vaccinia in individuals who have immunodeficiencies^{Footnote 47}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the Canadian Biosafety Handbook.

Immunization

Many VACV strains were developed and used in different countries as vaccines during the global smallpox eradication campaign initiated in 1967^{Footnote 22Footnote 23}. Routine VACV immunization against smallpox was discontinued in Canada in 1972^{Footnote 48}. In Canada, Imvamune, a non-replicating third-generation smallpox vaccine, and ACAM2000, a replicating-competent smallpox vaccine, are currently available^{Footnote 19Footnote 49Footnote 50Footnote 51}. While vaccination is available and is recommended for those at high risk, it’s not recommended for the general public^{Footnote 48}.

Note: More information on the medical surveillance program can be found in the Canadian Biosafety Handbook, and by consulting the Canadian Immunization Guide.

Prophylaxis

The National Advisory Committee on Immunization (NACI) recommends that Imavamune, as Pre-Exposure Prophylaxis (PrEP), be offered to personnel working with replicating orthopoxvirus that pose a risk to human health (such as VACV) in laboratory settings and who are at high risk of occupational exposure, as well as individuals at high risk^{Footnote 52}. Prophylactic VIG may also be used in individuals with contraindications to smallpox vaccination who are exposed to an Orthopoxvirus^{Footnote 47}.  

Note: More information on prophylaxis, as part of the medical surveillance program, can be found in the Canadian Biosafety Handbook.

Section VI – Laboratory hazard

Laboratory-acquired infections

VACV is considered a significant cause of laboratory-acquired infections (LAI), with 31 reported globally^{Footnote 53}. The root causes of these LAIs include accidental needlestick injuries, eye splashes (ocular exposure), and inhalation^{Footnote 15Footnote 33Footnote 54}.

Note: Please consult the Canadian Biosafety Standard and Canadian Biosafety Handbook for additional details on requirements for reporting exposure incidents.

Sources/specimens

VACV can be found in feces, blood (including serum), respiratory secretions and swabs (including nasopharyngeal and oropharyngeal swabs), lesion fluid and crusts (including skin samples), and milk^{Footnote 10Footnote 14Footnote 15Footnote 24Footnote 26Footnote 27Footnote 29Footnote 32Footnote 46Footnote 55}.

Primary hazards

Exposure of mucous membranes and/or broken skin to infectious material is the primary hazard associated with exposure to VACV^{Footnote 28Footnote 32}.

Special hazards

Work with experimentally or naturally infected animals or their wastes/secretions may present as a special hazard^{Footnote 4Footnote 10Footnote 24Footnote 32Footnote 46}.

Section VII – Exposure controls/personal protection

Risk group classification

VACV is a Risk Group 2 Human Pathogen and a Risk Group 2 Animal Pathogen^{Footnote 3Footnote 56}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the Canadian Biosafety Standard for work involving infectious or potentially infectious materials, animals, or cultures are required.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the Canadian Biosafety Standard are to be followed. The personal protective equipment could include the use of a labcoat and dedicated footwear (e.g., boots, shoes) or additional protective footwear (e.g., boot or shoe covers) where floors may be contaminated (e.g., animal cubicles, post mortem rooms), gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.  

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes are to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes are to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

For diagnostic laboratories handling primary specimens that may contain VACV, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time between the surface and the disinfectant before clean up (Canadian Biosafety Handbook).

Disposal

All materials/substances that have come in contact with the regulated materials to be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (Canadian Biosafety Handbook).

Storage

The applicable Containment Level 2 requirements for storage outlined in the Canadian Biosafety Standard are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with Orthopoxvirus vaccinia require a Pathogen and Toxin licence issued by the Public Health Agency of Canada. O. vaccinia is a terrestrial animal pathogen in Canada; therefore, its importation requires an import permit under the authority of the Health of Animals Regulations (HAR). The PHAC issues a “Pathogen and Toxin Licence document” for both a Human Pathogen and Toxin Licence and HAR importation permit.

The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogens and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Act and Transportation of Dangerous Goods Regulations

Last file update

May, 2025

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

Copyright © Public Health Agency of Canada, 2025, Canada         

References