Vaccination Strategies after Elimination of Poliomyelitis

说明（由申请人提供）：1988年世界卫生大会确定的一项目标，即在全球消灭脊髓灰质炎，有可能在今后五年内实现。在过去20年中，脊髓灰质炎病例急剧减少，从1988年估计的35万例减少到2004年的1300例以下，减少幅度超过99%。然而，最近发现的能够引起麻痹性脊髓灰质炎的循环强毒疫苗衍生脊髓灰质炎病毒（VDPV）威胁到根除脊髓灰质炎。此外，众所周知的三种Sabin血清型的点突变与疫苗相关性麻痹性脊髓灰质炎（VAPP）的发生有关。因此，一旦根除脊髓灰质炎，在全球范围内立即停止口服脊髓灰质炎疫苗（OPV）的使用是一个高度优先事项。了解脊髓灰质炎疫苗，特别是VDPV和VAPP的循环动力学，以及人类免疫缺陷病毒（HIV）感染对病毒脱落和灭活脊髓灰质炎疫苗（IPV）免疫原性的影响，对于制定根除后疫苗接种政策至关重要。关于IPV方案免疫原性的信息对于评估IPV是否可用于控制艾滋病毒高流行地区可能的根除后疫情非常重要。对于世界卫生组织正在考虑的根除后疫苗接种方案进行评估，缺乏关键数据，特别是在免疫缺陷个体中，这些个体可能比免疫功能正常的人更长时间地排出更多的VAPP和VDPV。我们建议及时提供数据，评估发展中国家健康和免疫缺陷人群接种脊髓灰质炎疫苗后脊髓灰质炎病毒、VAPP和VDPV的脱落和传播情况，以及在卫生条件差的健康和免疫缺陷婴儿中评估疫苗方案的免疫原性和粘膜免疫，这可能影响脊髓灰质炎病毒的免疫原性。拟议的研究将在生活在津巴布韦Chitungwiza的艾滋病毒感染和未感染的婴儿中进行，艾滋病毒血清阳性率为20%，以解决在为世界发展中地区设计脊髓灰质炎疫苗接种战略方面的具体差距。描述。麻痹性脊髓灰质炎可能很快就会被根除。然而，由脊髓灰质炎活疫苗引起的脊髓灰质炎可能发生，并可能威胁到根除脊髓灰质炎的努力。我们提出战略，以确定艾滋病毒感染对发展中国家消灭脊髓灰质炎战略的影响，并研究在全世界消灭脊髓灰质炎中使用灭活脊髓灰质炎疫苗。

DESCRIPTION (provided by applicant): The global eradication of poliomyelitis, a goal set by the World Health Assembly in 1988, may likely be achieved within the next five years. Cases of poliomyelitis have decreased dramatically in the last 20 years, from an estimated 350,000 cases in 1988 to under 1300 in 2004 - a greater than 99% reduction. However, the recent discovery of circulating virulent vaccine derived polioviruses (VDPV), capable of causing paralytic poliomyelitis, threatens eradication. In addition, well-known point mutations of the three Sabin serotypes are associated with development of vaccine-associated paralytic poliomyelitis (VAPP). Thus, global cessation of oral polio vaccine (OPV) use as soon as eradication occurs is a high priority. Understanding the dynamics of circulation of OPV, and especially of VDPV and VAPP, and the impact of human immunodeficiency virus (HIV) infection on viral shedding and on the immunogenicity of inactivated polio vaccine (IPV), is critical for the development of post-eradication vaccination policies. Information about the immunogenicity of IPV regimens is important to assess whether IPV can be used to control potential post-eradication outbreaks in areas of high HIV prevalence. There is a lack of critical data, especially among immunodeficient individuals who may shed more VAPP and VDPV for longer periods than those with normal immune function, to evaluate post-eradication vaccination options being considered by the World Health Organization. We propose to provide data, in a timely fashion, to evaluate the shedding and transmission of OPV, VAPP and VDPV by healthy and immunodeficient populations given OPV in a developing country, and to assess the immunogenicity and mucosal immunity of IPV regimens in healthy and immunodeficient infants living in poor sanitary conditions, which may affect IPV immunogenicity. The proposed studies will be carried among HIV- infected and uninfected infants living in Chitungwiza, Zimbabwe, with an HIV seroprevalence of 20%, to address specific gaps in designing polio vaccination strategies for developing areas of the world. Lay description. Paralytic poliomyelitis (polio) may soon be eradicated. However, polio caused by the live polio vaccine can occur and may threaten efforts to eradicated polio. We propose strategies to identify the effect of HIV infection on polio eradication strategies in a developing country and to study the use of a killed polio vaccine in eradication of poliomyelitis worldwide.