Laboratorio de Inmunobiología de las Mucosas, Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, Mexico.
Unidad de Producción y Experimentación de Animales de Laboratorio, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, Mexico.
Front Immunol. 2022 Mar 31;13:848054. doi: 10.3389/fimmu.2022.848054. eCollection 2022.
New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.
新的疫苗设计方法、平台和免疫策略可能会促进抗病毒黏膜效应和记忆反应，以减少接种个体的无症状感染和传播。在这里，我们研究了一种联合的肠外和黏膜免疫方案，以诱导局部和血清抗体反应，使用基于表位的抗原 3BT 和 NG19m。这些抗原分别针对重要的新兴和再出现病毒 PRRSV-2 和 SARS-CoV-2。我们评估了 3BT 蛋白的两个版本，该蛋白包含 PRRSV-2 的 GP5 包膜蛋白中的保守表位：可溶性和由重组杆状病毒 BacDual-3BT 表达。另一方面，NG19m 包含 SARS-CoV-2 的 S 蛋白的受体结合基序，仅作为可溶性重组蛋白进行评估。越南微型猪通过不同的接种途径进行免疫：皮下、鼻内或两者结合（s.c.-i.n.）。动物在血清和黏膜液中产生抗原结合和中和抗体，其浓度和活性模式因抗原和免疫方案而异。可溶性 3BT 是一种有效的免疫原，可在血清、鼻粘液和阴道拭子中诱导结合和中和抗体。载体免疫原 BacDual-3BT 诱导血清和黏膜中的结合抗体，但仅在鼻内接种时才发现 PRRSV-2 中和活性。NG19m 促进血清和黏膜结合抗体，其具有不同的中和活性。只有皮下免疫的动物的血清样本抑制 RBD-ACE2 相互作用，而鼻内或联合 s.c.-i.n. 方案接种的微型猪在上呼吸道和下呼吸道黏膜中产生微妙的中和体液反应。我们的结果表明，鼻内免疫单独或与基于表位的抗原的皮下给药联合使用，可产生局部和全身结合和中和抗体。需要进一步研究来评估诱导的反应预防感染和减少传播的能力。
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