Orthopoxvirus vaccines offer protection against a family of viruses with historical and current relevance. These vaccines played a monumental role in global health, notably contributing to the eradication of smallpox, a devastating disease that once claimed millions of lives. Today, their application extends to addressing emerging threats, such as mpox outbreaks, highlighting their continued importance in disease prevention and control.
Understanding Orthopoxviruses and the Vaccine’s Purpose
Orthopoxviruses are a genus of viruses within the Poxviridae family, known for causing various diseases in humans and animals. Historically, smallpox, caused by the variola virus, was the most well-known. Smallpox was a highly contagious and often deadly illness, characterized by a distinctive rash that could lead to severe disfigurement or death in approximately 3 out of 10 infected individuals.
While smallpox has been eradicated globally since 1980 due to widespread vaccination efforts, other orthopoxviruses continue to pose health concerns. Mpox, formerly known as monkeypox, is another significant orthopoxvirus that can infect humans, primarily found in central and western Africa. Mpox can cause flu-like symptoms, fever, and a rash. While generally less severe than smallpox, it can still lead to serious illness and, in rare cases, death. The orthopoxvirus vaccine, originally developed to combat smallpox, now plays a role in preventing mpox, especially during recent outbreaks where person-to-person transmission has been observed in non-endemic countries.
Types of Orthopoxvirus Vaccines
Two primary orthopoxvirus vaccines are available: Jynneos and ACAM2000. Jynneos, also known internationally as Imvamune or Imvanex, is a live, attenuated, non-replicating virus vaccine. It contains a weakened form of the vaccinia virus that cannot efficiently multiply in human cells, making it a safer option for certain populations. Jynneos is approved for individuals 18 years of age and older at high risk for smallpox or mpox infection.
ACAM2000 is a live, replication-competent vaccinia virus vaccine. This vaccine produces a localized infection at the vaccination site, a visible reaction known as a “take” that confirms successful vaccination. ACAM2000 is approved for active immunization against smallpox disease for individuals at high risk for smallpox infection. While initially designed for smallpox, it can be made available for mpox under an Expanded Access Investigational New Drug (EA-IND) protocol.
How the Vaccine Works and Administration
Orthopoxvirus vaccines function by introducing a modified or attenuated form of a vaccinia virus, a relative of the viruses that cause smallpox and mpox, into the body. This exposure stimulates the immune system to produce antibodies and T-cells, specialized immune cells that recognize and fight off future orthopoxvirus infections. The immune response provides protection against disease-causing viruses without causing full-blown illness.
Administration methods vary. Jynneos is typically given as two subcutaneous injections into the fat layer just beneath the skin, often in the upper arm. Doses are usually administered four weeks apart for best protection. For adults 18 and older, Jynneos can also be given intradermally, injected between the top layers of the skin, potentially in the forearm, upper back, or shoulder. This intradermal approach requires a smaller vaccine dose.
ACAM2000 is administered using a bifurcated needle to puncture the skin of the upper arm multiple times, a method known as percutaneous administration. This introduces the live vaccinia virus, which then replicates at the site, forming a lesion that scabs over and heals within several weeks. ACAM2000 is typically a single-dose vaccine. Proper care of the vaccination site is necessary until it fully heals, which can take up to six weeks, as the live vaccine virus can shed from the site and potentially spread to other body parts or individuals.
Who Should Consider Vaccination and Safety
Orthopoxvirus vaccination is recommended for specific groups at higher risk of exposure or severe outcomes. These include laboratory personnel who handle orthopoxviruses, military personnel, and healthcare workers who might care for infected patients or administer the ACAM2000 vaccine. During outbreaks, individuals at high risk of mpox exposure, such as those with multiple sex partners or a recent diagnosis of sexually transmitted diseases, are also advised to consider vaccination. Post-exposure vaccination, if given within 3 to 4 days of exposure, may prevent or reduce disease severity.
Common side effects are typically mild. For Jynneos, these may include pain, redness, swelling, or itching at the injection site, along with general symptoms like fever, fatigue, headache, muscle pain, and nausea. While rare, more serious side effects can occur. ACAM2000, a live, replicating vaccine, has a different safety profile. It carries a risk of more serious adverse events, such as myopericarditis (inflammation of the heart muscle or lining). ACAM2000 is contraindicated for pregnant individuals, those with weakened immune systems, or individuals with certain skin conditions like eczema, due to the potential for severe reactions like progressive vaccinia or eczema vaccinatum. Jynneos is a safer alternative for these populations because it is non-replicating and generally has fewer contraindications.