Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.
J Infect Dis. 2010 May 1;201(9):1353-60. doi: 10.1086/651560.
Despite the success of smallpox vaccination, the immunological correlates of protection are not fully understood. To investigate this question, we examined the effect of immunization with modified vaccinia Ankara (MVA) on subsequent challenge with replication-competent vaccinia virus (Dryvax).
Dryvax challenge by scarification was conducted in 36 healthy subjects who had received MVA (n = 29) or placebo (n = 7) in a previous study of doses and routes of immunization. Subjects were followed up for clinical take, viral shedding, and immune responses.
MVA administration attenuated clinical takes in 21 (72%) of 29 subjects, compared with 0 of 7 placebo recipients (P = .001). Attenuation was most significant in MVA groups that received 1 x 10(7) median tissue culture infective doses (TCID(50)) intradermally (P = .001) and 1 x 10(7) TCID(50) intramuscularly (P = .001). Both duration and peak titer of viral shedding were reduced in MVA recipients. Peak neutralizing antibody responses to vaccinia virus or MVA previously induced by MVA immunization were associated with attenuated takes (P = .02) and reduced duration (P = .001) and titer (P = .005) of viral shedding.
MVA immunization results in clinical and virologic protection against Dryvax challenge. Protection is associated with prior induction of neutralizing antibodies to MVA or vaccinia virus. MVA administered intradermally has protective and immunologic responses similar to those of a 10-fold-higher dose given subcutaneously.
尽管天花疫苗接种取得了成功，但保护的免疫相关性仍未完全了解。为了研究这个问题，我们研究了用改良安卡拉牛痘病毒（MVA）免疫接种对随后用复制型天花病毒（Dryvax）进行的挑战的影响。
在先前进行的剂量和免疫途径研究中，36 名健康受试者接受了 MVA（n = 29）或安慰剂（n = 7），通过划痕进行 Dryvax 挑战。对受试者进行临床随访、病毒脱落和免疫反应。
与 7 名安慰剂接受者中的 0 名相比（P =.001），29 名接受 MVA 治疗的受试者中有 21 名（72%）的临床发生率降低。在接受 1 x 10(7)中位数组织培养感染剂量（TCID(50)）皮内（P =.001）和 1 x 10(7)TCID(50)肌内（P =.001）的 MVA 组中，衰减最为显著。MVA 接受者的病毒脱落持续时间和峰值滴度均降低。先前由 MVA 免疫接种引起的对天花病毒或 MVA 的峰值中和抗体反应与减轻接种（P =.02）和减少病毒脱落的持续时间（P =.001）和滴度（P =.005）相关。
MVA 免疫接种可预防 Dryvax 挑战引起的临床和病毒学保护。保护与先前诱导的对 MVA 或天花病毒的中和抗体有关。皮内给予的 MVA 具有与皮下给予 10 倍高剂量相似的保护和免疫反应。
