A glycoprotein E gene-deleted bovine alphaherpesvirus 1 strain is attenuated and immunogenic for calves with passive immunity upon intranasal immunization

ABSTRACT: Vaccination has been used to prevent the losses associated with Bovine alphaherpesvirus 1 (BoHV-1) infection but passively acquired antibodies may compromise vaccine efficacy. Intranasal immunization (IN) of calves with modified live viral BoHV-1 vaccines has proven to overcome the acquired passive antibodies and confer adequate protection. Herein, we evaluated the safety and immunogenicity of a glycoprotein E-deleted Brazilian BoHV-1 strain (BoHV-1gEΔ) for IN immunization of calves. Ten 1-to-2 months-old calves with virus-neutralizing titers (VN) ranging from 2-64 were immunized IN with viable BoHV-1gEΔ (107.1 TCID50) and four remained as unvaccinated controls (VN titers 8-32). After IN immunization, calves presented a transient (2-6 days) mild nasal secretion and shed the vaccine virus in nasal secretions in low titers (<102.6TCID50/mL) for 4-8 days. Interestingly, the vaccinated calves did not show an increase in VN titers after vaccination. Rather, they presented a gradual reduction in serum VN antibodies in the following weeks - similarly to unvaccinated controls. Upon IN challenge with a virulent heterologous BoHV-1 strain at day 55 post-immunization (107.63TCID50), vaccinated calves shed significantly less virus from day 6 post-challenge onwards (p < 0.07) and for a shorter period of time than the controls (p < 0.0024). Importantly, both the duration and intensity of clinical signs were reduced in vaccinated animals. In addition, vaccinated calves showed an abrupt raise in VN titers post-challenge, indicating adequate immunological priming by vaccination. In summary, immunization of calves harboring passive antibodies with BoHV-1gEΔ by the IN route was able to prime the immunity to afford partial virological and clinical protection upon challenge.

摘要：疫苗接种一直被用于防控牛α疱疹病毒1型（Bovine alphaherpesvirus 1, BoHV-1）感染引发的相关损失，但被动获得的抗体可能会削弱疫苗的保护效果。已有研究证实，使用牛α疱疹病毒1型减毒活疫苗对犊牛进行鼻内免疫（Intranasal immunization, IN），可克服被动获得的抗体屏障并提供充足的保护作用。本研究评估了一株糖蛋白E缺失的巴西源牛α疱疹病毒1型毒株（BoHV-1gEΔ）用于犊牛鼻内免疫的安全性与免疫原性。选取10只日龄1~2个月、病毒中和抗体效价（VN）为2~64的犊牛，以活毒BoHV-1gEΔ（10^7.1 半数组织培养感染剂量，TCID50）进行鼻内免疫，另设4只未接种的空白对照（其VN效价为8~32）。鼻内免疫后，犊牛出现了一过性（2~6天）的轻度鼻腔分泌物症状，并在4~8天内以低滴度（<10^2.6 TCID50/mL）在鼻腔分泌物中排出疫苗毒。值得注意的是，免疫组犊牛在接种后并未出现VN效价升高的现象，反而在后续数周内出现血清VN抗体的逐步下降，与未接种的对照组犊牛表现一致。在免疫后第55天，以一株强毒异源牛α疱疹病毒1型毒株（10^7.63 TCID50）进行鼻内攻毒后，免疫组犊牛从攻毒后第6天起的病毒排出量显著低于对照组（p<0.07），且病毒排出持续时长更短（p<0.0024）。更为重要的是，免疫组动物的临床症状持续时长与严重程度均有所降低。此外，免疫组犊牛在攻毒后出现了VN效价的骤升，表明接种疫苗已实现了有效的免疫致敏。综上，通过鼻内免疫途径为携带被动抗体的犊牛接种BoHV-1gEΔ，可实现免疫致敏，在攻毒后能够提供部分病毒学与临床保护效果。