VACCINATION OF NEONATAL RHESUS MACAQUES W/ SHIV PROVIRAL DNA

使用 SHIV 原病毒 DNA 对新生恒河猴进行疫苗接种

• 批准号: 6277926
• 负责人: Marta L Marthas
• 金额: $ 8.13万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277926
• 关键词: AIDS; Mammalia; Primates; hematology; immunology; infection; inflammation; lymphatic system; model design /development; mother /infant health care; oral pharyngeal; vaccines; virus

Significance HIV transmission to infants by breast feeding after maternally acquired anti-HIVantibodies decline is well documented. Neonatal vaccination may reduce HIV transmission to children in developing nations where safe alternatives to breast feeding are not available. However, a safe and economical anti-HIV vaccine for neonates must also elicit immunity in the presence of maternal anti-HIV antibodies. Objectives Infection of newborn rhesus macaques with simian immunodeficiency virus is a well-established model for pediatric HIV infection and AIDS. This pilot study evaluated whether proviral DNA from the virulence-attenuated SHIV-33 (virus derived from a molecular clone that consists the HIV-1 SF-33 envelope gene in an otherwise SIV genome) could establish infection in neonates with transplacentally acquired anti-SIV antibodies. Results Three pregnant rhesus macaques were immunized twice intramuscularly during pregnancy with whole-inactivated SIV in adjuvant. After boosting, the dams produced high titer SIV-specific serum antibodies which were transferred to their infants. Four neonates with no anti-SIV antibodies served as controls. All seven infants were inoculated intramuscularly with 100 ug of SHIV-33 proviral DNA within 3 days of birth. Five of the seven infants became infected with SHIV-33 two infants with anti-SIV antibodies and three infants with no SIV antibodies. Virus levels remained low in all but one SHIV-infected animal and none developed any clinical signs of disease by 24 weeks of age. Thus, transplacentally acquired anti-SIV antibodies did not interfere with infection induced by inoculation of neonates with SHIV-33 proviral DNA. These results suggest that a live-attenuated HIV DNA might be developed as a vaccine that could establish infection even in infants with maternally-derived anti-HIV antibodies. Future Directions At 1 year of age each of the five animals infected with live-attenuated SHIV-33 will be inoculated orally with SIVmac239 to determine whether neonatal vaccination can provide long-term protection against virulent SIV. KEYWORDS Pediatric simian AIDS, oral SIV transmission, perinatal HIV transmission, neonatal immunization, live-attenuated vaccine

通过母乳喂养，艾滋病毒向婴儿的显着性传播 母体获得的抗动物下降有充分的记录。 新生儿疫苗接种可以减少对儿童的HIV传播 没有安全替代母乳喂养替代品的发展中国家 可用的。 但是，一种安全且经济的抗HIV疫苗 新生儿还必须在孕产妇存在的情况下引起免疫力 抗HIV抗体。 新生儿恒河猕猴的目标感染 伴有猿猴免疫缺陷病毒是一个完善的模型 小儿艾滋病毒感染和艾滋病。 这项试验研究评估了是否 来自毒力衰减的SHIV-33的病毒DNA（病毒源自源自 一个分子克隆，该克隆是HIV-1 SF-33包膜基因 否则SIV基因组）可以在新生儿中建立感染 移植获得的抗SIV抗体。 结果三个怀孕 猕猴在怀孕期间两次免疫两次 佐剂全活化的SIV。 加强后，大坝 产生高滴度SIV特异性血清抗体 转移给婴儿。 四个没有抗Siv的新生儿 抗体用作对照。 所有七个婴儿都接种了 肌肉内用100 ug的SHIV-33病毒DNA在3天内 出生。 七个婴儿中有五名被Shiv-33感染了两个 具有抗SIV抗体和三个无SIV的婴儿的婴儿 抗体。 病毒水平除了一个湿av感染 动物和没有人在24周的 年龄。 因此，接受的抗SIV抗体没有 干扰因接种新生儿而引起的感染 SHIV-33前病毒DNA。 这些结果表明活着的 HIV DNA可能被开发为可能建立感染的疫苗 即使在具有母体衍生的抗HIV抗体的婴儿中。 未来 五只动物中的1岁的指示 实时侵蚀的Shiv-33将与SIVMAC239口服接种 确定新生儿疫苗接种是否可以长期提供 防止有毒的SIV。 关键词小儿猿猴艾滋病，口腔 SIV传播，围产期HIV传播，新生儿免疫， 实时疫苗