美國國家衛生研究院開發的愛滋病毒抗體在概念驗證研究中保護動物
2024 年 1 月 17 日星期三/新聞發布/媒體諮詢
HIV-1 病毒顆粒（紅色）從慢性感染的 H9 細胞（藍色）片段中出芽和複製的透射電子顯微照片。 顆粒處於不同的成熟階段；弧形/半圓形是已開始形成但仍是細胞一部分的未成熟顆粒。未成熟顆粒緩慢地將形態轉變為墊 / NIAID
在一項安慰劑對照的概念驗證研究中，三種不同的 HIV 抗體各自獨立地保護猴子免於感染猿猴 HIV (SHIV)，該研究旨在為人類預防性 HIV 疫苗的開發提供資訊。這些抗體——一種人類廣泛中和抗體和兩種從先前接種疫苗的猴子中分離出來的抗體——以融合肽為目標，融合肽 (the fusion peptide) 是愛滋病毒表面蛋白上的一個位點，有助於病毒與細胞融合進入細胞。這項研究發表在《科學轉化醫學》上，由美國國家衛生研究院下屬的國家過敏和傳染病研究所 (NIAID) 疫苗研究中心 (VRC) 領導。
靶向融合胜肽的抗體可以在體外（即活體體外的試管或培養皿中）中和多種HIV病毒株。 NIAID VRC 從一名用於研究的愛滋病毒感染者身上捐血樣本分離出了一種融合胜肽導向的人類抗體，稱為 VRC34.01。他們還從恒河猴（一種具有與人類相似的免疫系統的猴子）中分離出兩種抗體，恒河猴之前接受過旨在產生融合胜肽導向抗體的疫苗方案。證明這些抗體可以保護動物將驗證融合肽作為人類疫苗設計的目標。 SHIV 攻擊（向恒河猴施用感染劑量的 SHIV）是一種廣泛使用的動物模型，用於評估 HIV 抗體和疫苗的性能。
在這項研究中，四組中的每組恒河猴接受了一種抗體的單次靜脈輸注——2.5或10毫克/公斤體重劑量的VRC34.01，或兩種疫苗引發的恒河猴抗體中的一種－－而其他猴子則接受安慰劑輸注。為了確定抗體的保護作用，每隻猴子在輸注已知對融合胜肽導引抗體敏感的 SHIV 株五天後接受攻擊。
所有接受安慰劑注射的猴子在挑戰後都感染了 SHIV。在接受 VRC34.01 輸注的猴子中，在接受 10 mg/kg 劑量的猴子中沒有感染 SHIV，而接受 2.5 mg/kg 劑量的猴子中有 25% 感染了 SHIV。在那些接受疫苗引發恒河猴抗體的猴子中，接受 DFPH-a.15 抗體的猴子沒有感染 SHIV，而接受 DF1W-a.01 抗體的猴子中有 25% 感染了 SHIV。隨著時間的推移，接受 DFPH-a.15 的動物血液中的抗體濃度下降。 30 天后，這些動物再次受到攻擊，看看較低濃度的抗體是否會降低保護作用，其中一半感染了 SHIV。
研究的三種抗體均提供了統計上顯著的針對 SHIV 的保護，且效果是劑量依賴性的，也就是說，在血液中抗體濃度較高的猴子中效果最高。
這組作者說，這些發現證明了融合胜肽導引抗體可以提供對 SHIV 的保護，並有助於確定疫苗產生保護作用所需的抗體濃度。他們認為，他們對某些動物疫苗引發抗體的發現支持進一步設計針對融合胜肽的預防性愛滋病疫苗概念。他們的結論是，針對 HIV 融合胜肽的有效 HIV 疫苗可能需要透過產生多種融合胜肽導向的抗體來擴展本研究中使用的概念。這對流通中的多種多樣的愛滋病毒變種將增加疫苗保持預防作用的可能性。
文章來源：
A Pegu et al. 針對 HIV 包膜上的融合胜肽的抗體可以保護恒河猴免受黏膜 SHIV 攻擊。 《科學轉譯醫學 》DOI：10.1126/scitranslmed.adh9039 (2024)
Richard Koup 醫學博士、NIAID VRC 副主任兼免疫學科主任可以討論這項研究。
如需安排採訪，請聯絡 NIAID 新聞與科學寫作分部，電話：(301) 402-1663，NIAIDNews@niaid.nih.gov（連結會以電子郵件傳送）。
NIAID 在 NIH、全美乃至全世界進行並支持研究，以研究傳染病和免疫介導疾病的原因，並開發更好的方法來預防、診斷和治療這些疾病。 新聞稿、概況介紹和其他 NIAID 相關資料可在 NIAID 網站上取得。
關於美國國立衛生研究院 (NIH)：NIH，美國的醫療機構
NIH-developed HIV antibodies protect animals in proof-of-concept study
Wednesday, January 17, 2024/ NEWS RELEASES / Media Advisory
Transmission electron micrograph of HIV-1 virus particles (red) budding and replicating from a segment of a chronically infected H9 cell (blue). Particles are in various stages of maturity; arc/semi-circles are immature particles that have started to form but are still part of the cell. Immature particles slowly change morphology into mat NIAID
Three different HIV antibodies each independently protected monkeys from acquiring simian-HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform development of a preventive HIV vaccine for people. The antibodies—a human broadly neutralizing antibody and two antibodies isolated from previously vaccinated monkeys—target the fusion peptide, a site on an HIV surface protein that helps the virus fuse with and enter cells. The study, published in Science Translational Medicine, was led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Antibodies that target the fusion peptide can neutralize diverse strains of HIV in vitro, that is, in a test tube or culture dish outside of a living organism. The NIAID VRC isolated a fusion peptide-directed human antibody, called VRC34.01, from a person living with HIV who donated blood samples for research. They also isolated two antibodies from rhesus macaques—a species of monkey with immune systems like humans’—who previously had received a vaccine regimen designed to generate fusion peptide-directed antibodies. Demonstrating that these antibodies protect animals would validatethe fusion peptide as a target for human vaccine design. SHIV challenge—administering an infective dose of SHIV—to rhesus macaques is a widely used animal model for assessing the performance of HIV antibodies and vaccines.
In this study, rhesus macaques in each of four groups received a single intravenous infusion of one type of antibody—a 2.5 or 10 mg/kg of bodyweight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies—and other monkeys received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after infusion with a strain of SHIV known to be sensitive to fusion peptide-directed antibodies.
All monkeys that received a placebo infusion acquired SHIV following the challenge. Among monkeys that received VRC34.01 infusions, none receiving the 10 mg/kg dose and 25% of those receiving the 2.5 mg/kg dose acquired SHIV. Of those that received the vaccine-elicited rhesus macaque antibodies, no monkeys receiving the antibody called DFPH-a.15 acquired SHIV, and 25% of those receiving the antibody called DF1W-a.01 acquired SHIV. Over time, the concentration of antibodies in the blood of animals that received DFPH-a.15 declined. Those animals were re-challenged 30 days later to see if the lower concentration of antibodies had a decreased protective effect, and half of them acquired SHIV.
The three antibodies studied each provided statistically significant protection from SHIV, and the effect was dose dependent, that is, highest in monkeys with greater antibody concentrations in their blood.
According to the authors, these findings represent the proof-of-concept that fusion peptide-directed antibodies can provide protection against SHIV and help determine the concentration of antibodies a vaccine would need to generate to be protective. They suggest that their findings on vaccine-elicited antibodies in some animals support further work to design preventive HIV vaccine concepts targeting the fusion peptide. They conclude that an effective HIV vaccine targeting the HIV fusion peptide likely will need to expand upon the concepts used in this study, by generating multiple varieties of fusion peptide-directed antibodies. This would increase the likelihood that the vaccine could maintain a preventive effect across the vastly diverse HIV variants in circulation.
Article
A Pegu et al. Antibodies targeting the fusion peptide on the HIV envelope provide protection to rhesus macaques against mucosal SHIV challenge. Science Translational Medicine DOI: 10.1126/scitranslmed.adh9039 (2024)
Richard Koup, M.D., NIAID VRC Deputy Director and Immunology Section Chief, is available to discuss this research.
To schedule interviews, please contact the NIAID News & Science Writing Branch, (301) 402-1663, NIAIDNews@niaid.nih.gov(link sends e-mail).
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