Abstract
I
Historically, replicating smallpox vaccines, such as Dryvax, ACAM2000, and LC16m8, have been associated with adverse events ranging from frequent, though self-limiting, events like autoinoculation to life-threating, albeit rare, events including eczema vaccinatum and encephalitis.1,2 More recently, cardiac complications, including a high incidence of myo-/pericarditis, have been associated with vaccination with replicating smallpox vaccines. This association was first observed during the 2003 US military and civilian smallpox vaccination programs.3,4 Cardiac monitoring during the development of ACAM2000 detected myo-/pericarditis at a rate of 1 in every 175 vaccinees. 5
Based on this experience, the US FDA has required Bavarian Nordic to conduct extensive cardiac screening and surveillance in nearly all of the clinical studies that have been conducted during the development of IMVAMUNE (IMVANEX). In these trials, study participants have been closely monitored for onset of cardiac signs or symptoms, ECG changes, and elevation of cardiac enzymes.
None of the cardiac findings associated with replicating smallpox vaccines was observed with IMVAMUNE (IMVANEX) in any of the 3,432 subjects vaccinated in completed clinical trials so far. Furthermore, currently ongoing clinical trials have more than doubled the total population having received IMVAMUNE (IMVANEX) (N>7,300). In the currently ongoing, placebo-controlled Phase III trial, all 4,005 enrolled participants underwent a thorough screening with a special focus on cardiologic aspects. Close cardiac monitoring has been performed throughout the trial. Although the study is still blinded, not a single confirmed case of myo-/pericarditis has been reported.
Furthermore, a recent review of cardiac adverse events in healthy adults receiving MVA-based vaccines failed to detect a single cardiac adverse event in 382 patients. 6 Indeed, as noted by Elizaga and colleagues, over the past decade numerous studies using attenuated recombinant poxvirus vaccines have been conducted with no reported events consistent with evidence of myo-/pericarditis.
While it is true that the “absence of evidence is not evidence of absence,” the assertion by Drs. Henderson and Arita that incomplete studies of IMVAMUNE (IMVANEX) indicate possible risks of myocardial effects is simply unfounded. Your readers should be informed of the important cardiac risks associated with replicating smallpox vaccines and the studies, which are still in progress, that are aimed at establishing whether nonreplicating smallpox vaccines like IMVAMUNE (IMVANEX) may actually avoid these and other potential complications.