Smallpox Vaccine Appears Safe and Immunogenic

Smallpox Vaccine Appears Safe and Immunogenic

SAITAMA, Japan, March 10 — A live attenuated tissue-cultured smallpox vaccine — first used in children in the 1970s — is safe and immunogenic in adults, researchers here said.

The “third-generation” LC16m8 vaccine showed an immune response in nearly 95% of previously unvaccinated participants and in about 87% of those who had earlier been immunized, according to Yasuhiro Kanatani, M.D., Ph.D., of the National Defense Medical College in Saitama, Japan, and colleagues.

 

In a cohort of 3,221 participants, the researchers saw only two “possibly severe” adverse events that might have been caused by the vaccine, the researchers reported in the March 11 issue of the Journal of the American Medical Association.

 

Aside from those two cases — one allergic dermatitis and one erythema multiforme — the researchers saw no signs of such adverse events as progressive or generalized vaccinia, encephalitis, or symptomatic myopericarditis.

 

Although smallpox has been eradicated worldwide, stocks exist for research in both the U.S. and Russia and there has been concern that bioterrorists could get their hands on — and unleash — the virus.

 

In the U.S., two vaccines are licensed, an older medication called Dryvax and ACAM2000, which was approved in 2007. But serious side effects — including encephalitis and endocarditis — have been reported for both.

 

LC16m8 has been licensed in Japan for 25 years and a U.S. phase I/II trial, reported in 2005, found promising immunogenicity with few side effects. (See: ASM: Investigational Smallpox Vaccine Shows Fewer Adverse Events)

 

In the 1970s, more than 100,000 Japanese children were given the vaccine, with good immune responses and few adverse events, Dr. Kanatani and colleagues said.

 

For this study, they examined clinical and immunological responses in adults, including 1,529 who had not previously been vaccinated.

 

The participants were examined 10 to 14 days after vaccination to determine if they had developed a major skin reaction, or “take,” and monitored for adverse events for 30 days.

 

Neutralizing antibody responses in a subset of 200 participants were assessed using a plaque-reduction neutralization test 30 days after vaccination.

 

The researchers found:

 

  • Nearly 95% of vaccine-naive participants — 94.4% or 1,443 of 1,529 — had a “take,” compared with 86.6% (or 1,465 of 1692) of those who had previously been vaccinated.
  • Seroconversion was studied in 45 vaccine-naive participants, but four did not “take” and were excluded. Among the remaining 41 volunteers, 37 (or 90.2%) had neutralizing antibody responses that indicated seroconversion.
  • Among 155 previously vaccinated participants, neutralizing antibody responses indicated an effective booster response in 93 (or 60%).
  • Most adverse events occurred with a frequency of less than 1%, except that 9% of participants reported swelling of axillary lymph nodes and 2% had low-grade fever.

 

The researchers noted that the study was too small to rule out severe adverse events, but they observed none — “consistent with past studies in children.”

 

They also pointed out that myopericarditis — observed in the U.S. program — has been a major concern surrounding adult smallpox vaccination.

 

“The sample size was limited to sufficiently verify the absence of myopericarditis,” the researchers said. “In addition, asymptomatic myopericarditis could not be excluded, because the sensitivity of ECG and measurement of troponin T levels 30 days post-vaccination is limited. A more appropriate time to perform ECG and quantify troponin T levels to detect myopericarditis is seven to 14 days after vaccination.”

 

The vaccine “appears to be a viable alternative to first-, second-, and other third-generation vaccines in a smallpox preparedness program,” they concluded.

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