A polyvalent Clade B virus-like particle HIV vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus Infection in macaques and primes for virus-amplified immunity.
A polyvalent Clade B virus-like particle HIV vaccine combined with partially protective oral preexposure prophylaxis prevents simian-human immunodeficiency virus Infection in macaques and primes for virus-amplified immunity.
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多价 B 分支病毒样颗粒 HIV 疫苗与部分保护性口服暴露前预防相结合，可预防猕猴中的猿猴-人类免疫缺陷病毒感染，并引发病毒增强免疫力。
DOI：
10.1089/aid.2014.0030
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发表时间：
2014
影响因子：
1.5
通讯作者：
Smith,JamesM
中科院分区：
文献类型：
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作者：
Ross,TedM;Pereira,LaraE;Luckay,Amara;McNicholl,JanetM;García-Lerma,JGerardo;Heneine,Walid;Eugene,HermanciaS;Pierce-Paul,BrookeR;Zhang,Jining;Hendry,RMichael;Smith,JamesM
在人体试验中，疫苗接种和暴露前预防 (PrEP) 抗逆转录病毒药物只能部分保护免受 HIV-1 感染。口服 Truvada（恩曲他滨/富马酸替诺福韦二吡呋酯）已被 FDA 批准作为 PrEP，但部分依从会降低疗效。如果与生物医学预防 (CBP) 结合起来，HIV 疫苗可以在 PrEP 依从性较低时提供保护，而 PrEP 可以防止疫苗突破。口服 PrEP 与 HIV 疫苗相结合的功效尚未在人体中进行评估。我们确定了将 DNA/病毒样颗粒 (VLP) 疫苗与部分有效的间歇性 PrEP 相结合对印度恒河猴 (RM) 的功效。 8 名 RM 接受了编码 4 个 HIV-1 B 分支初级分离株 Env 和 SIVmac239 Gag 的 5 个 DNA 质粒的肌肉内接种（第 0 周和第 4 周），然后肌肉内和鼻内接种同源 Gag VLP 和 4 个 Env VLP（第 12、16 和 53 周）。在第 61 周，我们开始每周进行异源 SHIV162p3 (10 TCID50) 直肠暴露，并在每次暴露前 2 小时和暴露后 22 小时口服 Truvada（TDF，22 mg/kg；FTC 20 mg/kg）。这种 PrEP 方案之前已证明有 50% 的功效。五个对照（无疫苗、无 PrEP）每周接受 SHIV162p3。所有对照在平均四次暴露后均被感染；平均峰值血浆病毒载量（VL）为3.9×107vRNA拷贝/ml。 CBP 保护了八名 RM 中的七名 (87.5%)。受感染的 CBP RM 的峰值 VL 降低为 8.8×105copies/ml。 PrEP 期间的 SHIV 暴露会放大受保护 RM 中的 Gag 和 Env 抗体滴度。这些结果表明，口服 PrEP 与 HIV 疫苗相结合可以增强对 HIV-1 感染的保护。
Vaccination and preexposure prophylaxis (PrEP) with antiretrovirals have shown only partial protection from HIV-1 infection in human trials. Oral Truvada (emtricitabine/tenofovir disoproxil fumarate) is FDA approved as PrEP but partial adherence reduces efficacy. If combined as biomedical preventions (CBP), an HIV vaccine could protect when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. The efficacy of combining oral PrEP with an HIV vaccine has not been evaluated in humans. We determined the efficacy of combining a DNA/virus-like particle (VLP) vaccine with partially effective intermittent PrEP in Indian rhesus macaques (RM). Eight RM received intramuscular inoculations of five DNA plasmids encoding four HIV-1 Clade B primary isolate Envs and SIVmac239 Gag (at weeks 0 and 4), followed by intramuscular and intranasal inoculations of homologous Gag VLPs and four Env VLPs (at weeks 12, 16, and 53). At week 61, we initiated weekly rectal exposures with heterologous SHIV162p3 (10 TCID50) along with oral Truvada (TDF, 22 mg/kg; FTC 20 mg/kg) dosing 2 h before and 22 h after each exposure. This PrEP regimen previously demonstrated 50% efficacy. Five controls (no vaccine, no PrEP) received weekly SHIV162p3. All controls were infected after a median of four exposures; the mean peak plasma viral load (VL) was 3.9×107vRNA copies/ml. CBP protected seven of eight (87.5%) RM. The one infected CBP RM had a reduced peak VL of 8.8×105copies/ml. SHIV exposures during PrEP amplified Gag and Env antibody titers in protected RM. These results suggest that combining oral PrEP with HIV vaccines could enhance protection against HIV-1 infection.