Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 1100 Fairview Ave. N., PO Box 19024, Seattle, WA 98109, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 1100 Fairview Ave. N., PO Box 19024, Seattle, WA 98109, USA; Department of Applied Mathematics, University of Washington, Seattle, WA, 1959 NE Pacific St, Box 357155, Seattle, WA 98195, USA.
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 1100 Fairview Ave. N., PO Box 19024, Seattle, WA 98109, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, 1100 Fairview Ave. N., PO Box 19024, Seattle, WA 98109, USA.
EBioMedicine. 2015 Nov 5;2(12):2062-9. doi: 10.1016/j.ebiom.2015.11.009. eCollection 2015 Dec.
As HIV-1 envelope immune responses are critical to vaccine related protection, most candidate HIV vaccines entering efficacy trials are based upon a clade specific design. This need for clade specific vaccine prototypes markedly reduces the implementation of potentially effective HIV vaccines. We utilized a mathematical model to determine the effectiveness of immediate roll-out of a non-clade matched vaccine with reduced efficacy compared to constructing clade specific vaccines, which would take considerable time to manufacture and test in safety and efficacy trials. We simulated the HIV epidemic in San Francisco (SF) and South Africa (SA) and projected effectiveness of three vaccination strategies: i) immediate intervention with a 20-40% vaccine efficacy (VE) non-matched vaccine, ii) delayed intervention by developing a 50% VE clade-specific vaccine, and iii) immediate intervention with a non-matched vaccine replaced by a clade-specific vaccine when developed. Immediate vaccination with a non-clade matched vaccine, even with reduced efficacy, would prevent thousands of new infections in SF and millions in SA over 30 years. Vaccination with 50% VE delayed for five years needs six and 12 years in SA to break-even with immediate 20 and 30% VE vaccination, respectively, while not able to surpass the impact of immediate 40% VE vaccination over 30 years. Replacing a 30% VE with a 50% VE vaccine after 5 years reduces the HIV acquisition by 5% compared to delayed vaccination. The immediate use of an HIV vaccine with reduced VE in high risk communities appears desirable over a short time line but higher VE should be the pursued to achieve strong long-term impact. Our analysis illustrates the importance of developing surrogate markers (correlates of protection) to allow bridging types of immunogenicity studies to support more rapid assessment of clade specific vaccines.
由于 HIV-1 包膜免疫反应对疫苗相关保护至关重要，因此大多数进入疗效试验的候选 HIV 疫苗都是基于特定分支的设计。这种对特定分支疫苗原型的需求显著降低了潜在有效 HIV 疫苗的实施。我们利用数学模型来确定立即推出一种非分支匹配疫苗的效果，该疫苗的疗效（VE）比构建特定分支疫苗低，而构建特定分支疫苗需要相当长的时间在安全性和疗效试验中制造和测试。我们模拟了旧金山（SF）和南非（SA）的 HIV 流行情况，并预测了三种疫苗接种策略的效果：i）立即干预使用 20-40%VE 的非匹配疫苗，ii）通过开发 50%VE 的特定分支疫苗延迟干预，以及 iii）立即使用非匹配疫苗干预，当开发出特定分支疫苗时用其替代。立即接种非分支匹配疫苗，即使疗效降低，也将在 30 年内防止 SF 地区数千例新感染，在 SA 地区数百万例新感染。接种 50%VE 的疫苗延迟 5 年，分别需要 6 年和 12 年才能与立即接种 20%和 30%VE 疫苗相抵，同时在 30 年内无法超过立即接种 40%VE 疫苗的影响。在 5 年后用 50%VE 疫苗替代 30%VE 疫苗可将 HIV 获得率降低 5%，与延迟接种相比。在短时间内，在高风险社区中立即使用 VE 降低的 HIV 疫苗似乎是可取的，但应追求更高的 VE 以实现长期的强有力影响。我们的分析表明，开发替代标志物（保护相关性）的重要性，以允许免疫原性研究的类型桥接，从而支持更快速地评估特定分支疫苗。
