Vaccinia Virus · What Is It, Vaccines, Side Effects, and More

The vaccinia virus is a large, double-stranded DNA virus that belongs to the Poxvirus family. Poxviruses are capable of causing disease in both humans and animals, and all have a preference for infecting skin cells. Therefore, they typically cause febrile rash illnesses with characteristic skin lesions.   

Besides the vaccinia virus, major agents in the Poxvirus family include the variola virus, which causes smallpox infection, and the monkeypox (Mpox) virus. Because the vaccinia virus only causes mild infections in humans and can induce immunity against other viruses, it has been extensively studied to develop novel vaccines and as a tool for gene therapy. 

The vaccinia virus is best known for being the agent behind the smallpox vaccine. Smallpox was a highly contagious and often fatal disease that was eradicated in 1980 after years of a global vaccination campaign. In the United States, routine vaccination against smallpox ended in the 1970s. However, individuals with a high risk of occupational exposure to poxviruses (e.g., laboratory personnel and military workers) still receive the vaccine.  

There are currently two smallpox vaccines licensed in the United States, the ACAM2000™ and the JYNNEOS® vaccine, also known as Imvamune® or Imvanex®. The ACAM2000 vaccine contains the unmodified live vaccinia virus, so it can cause adverse reactions in individuals with a weakened immune system. On the other hand, the JYNNEOS vaccine is a live attenuated vaccine where the vaccinia virus has been weakened in the laboratory to make it less pathogenic but is still able to stimulate an immune response. The resulting attenuated virus is named modified vaccinia Ankara strain (MVA). The advantage of the JYNNEOS vaccine is that it can be administered to individuals at risk for vaccinia complications and it has also been proven to be effective against the monkeypox (Mpox) virus.  

Nowadays, recombinant vaccinia technology is being studied for the development of vaccines against malaria, HIV infection, and hepatitis, as well as in the treatment of cancer. Live recombinant vaccines use attenuated vaccinia viruses as a vector to carry foreign genes encoding for the desired vaccine antigens. Because live recombinant vaccines act like a natural infection, they are capable of stimulating an effective immune response that may enable future immunity. 

Because the smallpox vaccine contains the live vaccinia virus, vaccinia virus can spread from one individual to another if they come in close contact with the vaccination site before it completely heals. It is also possible for the vaccinated person to spread the virus from the vaccination site to another part of their body through autoinoculation. Though rare, there have been reports of sexual transmission between recently vaccinated individuals and unvaccinated individuals. 

To avoid transmission of the vaccinia virus, vaccinated individuals are advised to wear protective bandages over the vaccination site until a scab has formed and fallen off. Recently vaccinated individuals should avoid contact with individuals at risk of vaccinia complications, such as young children, immunocompromised or pregnant individuals, and those with a history of atopic dermatitis (i.e., eczema).   

While it is not the main mechanism of transmission, vaccinia virus can also be transmitted to humans through contact with infected dairy cattle, usually by milking cows with active lesions without protective gloves. 

Vaccinia virus typically causes mild symptoms in humans, including weakness, fever, swelling of the lymph nodes, and skin lesions that may evolve into pus-filled vesicles or ulcerated lesions.  

When the vaccinia virus is inoculated through the smallpox vaccine, additional adverse reactions may occur. Common reactions to the smallpox vaccine include mild fever, fatigue, muscle aches, and headache, as well as soreness or redness at the site of injection. After 3 to 5 days of vaccination, a skin lesion may appear at the vaccination site. Over the first week, the lesion becomes larger and fills with pus, indicating that vaccination has been successful. The lesion dries out in the following weeks until a scab forms and eventually falls off, leaving a small, pitted scar.    

Although the smallpox vaccine is generally safe, some individuals may develop severe adverse reactions. For example, vaccinia virus can be spread to the eyes through autoinoculation, resulting in conjunctivitis or corneal damage. In people with weakened immune systems, the vaccination site may fail to heal, allowing the vaccinia virus to continue to replicate in the skin. This may result in a condition called progressive vaccinia, where the skin surrounding the vaccination site becomes infected and necrotic.  

The smallpox vaccine can also result in two diffuse skin conditions: generalized vaccinia and eczema vaccinatum. Generalized vaccinia is a benign skin rash with widespread skin lesions that are often self-limited among healthy individuals. On the other hand, eczema vaccinatum is a rare complication that causes an extensive rash followed by fever and swelling of the lymph nodes, and in severe cases, may be fatal. Eczema vaccinatum is more common in people with a history of eczema or atopic dermatitis, which is why the vaccine is contraindicated in these individuals.  

The smallpox vaccine is also contraindicated in pregnant individuals due to the risk of obstetric complications, such as miscarriage, stillbirth, or premature birth. In infants less than 12 months old, the smallpox vaccine may result in post-vaccinial central nervous system symptoms, characterized by headache, vomiting, altered mental status, lethargy, seizures, and coma. Finally, the smallpox vaccine may cause cardiac symptoms like angina; myocarditis, or inflammation of the heart muscle; and pericarditis, which is the inflammation of the outer layer of the heart. 

Diagnosis of vaccinia virus infection is made clinically in individuals with a compatible clinical presentation and a history of exposure to the smallpox vaccine or contact with a recently vaccinated person. In rural areas, the presence of compatible lesions and a history of recent contact with dairy cattle should also raise suspicion for vaccinia virus infection. Confirmation of the diagnosis may be achieved by culturing the lesion in the laboratory or detecting viral DNA. 

Treatment of vaccinia virus infections depends on the severity of the condition. Mild vaccinia virus infections can be managed with rest and analgesic medications like acetaminophen. According to the Centers for Disease Control and Prevention (CDC), severe vaccinia infections can be treated with intravenous immune globulin (IVIG), which is prepared from antibodies found in the serum of individuals who have received the smallpox vaccine. If the IVIG is not effective or readily available, other treatment options include antivirals such as tecovirimat (i.e., TPOXX®), cidofovir (i.e., Vistide®), and brincidofovir (i.e., Tembexa®). These antivirals are not specific to treat vaccinia virus, but they have been shown to reduce viral growth in laboratory testing. As a result, they are reserved to treat severe vaccinia infections and for emergency use in public health outbreaks.