Table 2.

Characteristics of first-, second- and third-generation smallpox vaccines.

Vaccine generation	Characteristics of vaccine	Potential Adverse Events
First (e.g., Dryvax, Aventis Pasteur Smallpox Vaccine, Lister, Tiantan/Temple of Heaven, and EM63 among others)	Vaccines used during the eradication campaign included several different strains of vaccinia virus. Nearly all were propagated in calf lymph. All first-generation vaccines used live, replication-competent virus. A successful vaccination produced a lesion at the site of administration that generated infectious virus.	•Risk of autoinoculation to other parts of the body as well as inadvertent transmission to other people. •Severe, life-threatening progressive or disseminated infection possible in persons with immunosuppression or certain skin conditions (e.g., atopic dermatitis). •Postvaccinial encephalitis, a rare but serious adverse event, particularly in children <2 years old (Jezek et al., 1988; Lane et al., 1970; Lane et al., 1969). •Myopericarditis observed among participants of clinical trials and smallpox vaccination programs, though the pathophysiology and clinical significance of this complication are unclear (Mora et al., 2009; Morgan et al., 2008). •Fetal vaccinia (Ryan et al., 2008).
Second (e.g., ACAM2000, Lister vaccine produced in primary rabbit kidney cells (RIVM), Elstree-BN, VV Lister/CEP, and CJ-50300)	Second-generation vaccines are propagated in tissue cell culture and produced under good manufacturing practices. As such, they have less risk of contamination with adventitious agents. However, second generation vaccines still contain live, replication-competent vaccinia virus and as such are assumed to present the same risk of adverse events as first-generation vaccines.	Same as above
Third (e.g., IMVAMUNE and LC16m8)	IMVAMUNE is derived from Modified Vaccinia Ankara (MVA), a vaccinia virus that has lost the ability to replicate in mammalian cells. Consequently, it does not produce a lesion at the site of vaccination and no longer presents a risk of autoinoculation, inadvertent transmission, or systemic spread. IMVAMUNE was developed for use in persons with increased risk factors for adverse events.	•Local signs and symptoms such as pain, erythema, induration, swelling, and pruritus at the administration site. •Systemic signs and symptoms have been reported, such as pyrexia, chills, fatigue, myalgia, headache, and nausea.