Single-Dose Injection of Human Neutralizing Antibody Against ZIKV Preserves Male Fertility and Protects against Lethal Infection.

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Hao Zhang, Ziyang Sheng, Feiyang Xue, Han Wang, Na Gao, Shiqi He, Yuetong Li, Dongying Fan, Peigang Wang, Lei Yu, Jing An
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Abstract

Zika virus (ZIKV) is a mosquito-transmitted flavivirus. Unlike other flavivirus members, ZIKV has a distinct tropism for the reproductive system. Previous studies have demonstrated that ZIKV has adverse impacts on the male reproductive system, particularly in testis and epididymis. However, no specific prophylactic and therapeutic agents are available against ZIKV till now. A human monoclonal antibody, 2B10, has been shown to be protective against microcephaly. Here, we intraperitoneally administered a single injection of 2B10 after ZIKV infection to explore its therapeutic potential on viral damage in testis and epididymis in both IFN-α/β and IFN-γ receptor-deficient (AG6) mouse and IFN-α/β receptor-deficient (A6) mouse models. The results showed that 2B10 significantly decreased the viremia and viral loads in organs in two types of male mice, markedly mitigated ZIKV-induced histo-morphologic disruption and inflammatory infiltration and maintained hormone levels. The integrity of tight junctions in the testis and epididymis was also maintained at normal levels by 2B10 administration. In long-term observation in ZIKV-infected A6 mice, 2B10 could confer effective protection of male fertility. In the AG6 model, 2B10 fully protected mice from lethal challenge. These results suggested that 2B10 provides effective protection in post-exposure therapy for ZIKV infection in mice. Since 2B10 is a human antibody, it might be a promising intervention candidate for maintaining male reproductive health during ZIKV infection in the endemic area.

单剂量注射人抗寨卡病毒中和抗体保护男性生育能力和预防致命感染。
寨卡病毒(ZIKV)是一种蚊子传播的黄病毒。与其他黄病毒成员不同,寨卡病毒对生殖系统有明显的倾向。以往的研究表明,寨卡病毒对男性生殖系统,特别是睾丸和附睾有不利影响。然而,目前尚无针对寨卡病毒的特异性预防和治疗药物。人单克隆抗体2B10已被证明对小头症有保护作用。本研究在ZIKV感染后腹腔单次注射2B10,探讨其对IFN-α/β和IFN-γ受体缺陷(AG6)小鼠和IFN-α/β受体缺陷(A6)小鼠模型睾丸和附睾病毒损伤的治疗潜力。结果表明,2B10可显著降低两种雄性小鼠器官内的病毒血症和病毒载量,显著减轻zikv诱导的组织形态学破坏和炎症浸润,维持激素水平。2B10给药后,睾丸和附睾紧密连接的完整性维持在正常水平。对感染zikv的A6小鼠进行长期观察,发现2B10能有效保护雄性生殖力。在AG6模型中,2B10完全保护小鼠免受致死攻击。这些结果提示2B10对小鼠寨卡病毒感染暴露后治疗具有有效的保护作用。由于2B10是一种人抗体,它可能是在寨卡病毒流行地区维持男性生殖健康的一种有希望的干预候选物。
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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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