Cervantes-Torres Jacquelynne, Cabello-Gutiérrez Carlos, Ayón-Núñez Dolores-Adriana, Soldevila Gloria, Olguin-Alor Roxana, Diaz Georgina, Acero Gonzalo, Segura-Velázquez René, Huerta Leonor, Gracia-Mora Isabel, Cobos Laura, Pérez-Tapia Mayra, Almagro Juan C, Suárez-Güemes Francisco, Bobes Raúl J, Fragoso Gladis, Sciutto Edda, Laclette Juan Pedro
School of Veterinary Medicine, Universidad Nacional Autónoma de México, Coyoacán, 04510, Mexico City, Mexico.
Biomedical Research Institute, Universidad Nacional Autónoma de México, Coyoacán, 04510, Mexico City, Mexico.
Appl Microbiol Biotechnol. 2024 Jan 27;108(1):179. doi: 10.1007/s00253-023-12927-0.
Several COVID-19 vaccines use adenovirus vectors to deliver the SARS-CoV-2 spike (S) protein. Immunization with these vaccines promotes immunity against the S protein, but against also the adenovirus itself. This could interfere with the entry of the vaccine into the cell, reducing its efficacy. Herein, we evaluate the efficiency of an adenovirus-vectored vaccine (chimpanzee ChAdOx1 adenovirus, AZD1222) in boosting the specific immunity compared to that induced by a recombinant receptor-binding domain (RBD)-based vaccine without viral vector. Mice immunized with the AZD1222 human vaccine were given a booster 6 months later, with either the homologous vaccine or a recombinant vaccine based on RBD of the delta variant, which was prevalent at the start of this study. A significant increase in anti-RBD antibody levels was observed in rRBD-boosted mice (31-61%) compared to those receiving two doses of AZD1222 (0%). Significantly higher rates of PepMix™- or RBD-elicited proliferation were also observed in IFNγ-producing CD4 and CD8 cells from mice boosted with one or two doses of RBD, respectively. The lower efficiency of the ChAdOx1-S vaccine in boosting specific immunity could be the result of a pre-existing anti-vector immunity, induced by increased levels of anti-adenovirus antibodies found both in mice and humans. Taken together, these results point to the importance of avoiding the recurrent use of the same adenovirus vector in individuals with immunity and memory against them. It also illustrates the disadvantages of ChAdOx1 adenovirus-vectored vaccine with respect to recombinant protein vaccines, which can be used without restriction in vaccine-booster programs. KEY POINTS: • ChAdOx1 adenovirus vaccine (AZD1222) may not be effective in boosting anti-SARS-CoV-2 immunity • A recombinant RBD protein vaccine is effective in boosting anti-SARS-CoV-2 immunity in mice • Antibodies elicited by the rRBD-delta vaccine persisted for up to 3 months in mice.
几种新冠疫苗利用腺病毒载体来递送严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突（S）蛋白。用这些疫苗进行免疫接种可促进针对S蛋白的免疫，但同时也针对腺病毒本身。这可能会干扰疫苗进入细胞，降低其效力。在此，我们评估一种腺病毒载体疫苗（黑猩猩ChAdOx1腺病毒，AZD1222）与一种不含病毒载体的基于重组受体结合域（RBD）的疫苗相比，在增强特异性免疫方面的效率。用AZD1222人用疫苗免疫的小鼠在6个月后接受加强免疫，加强疫苗要么是同源疫苗，要么是基于本研究开始时流行的德尔塔变体RBD的重组疫苗。与接受两剂AZD1222的小鼠（0%）相比，接受rRBD加强免疫的小鼠（31 - 61%）中抗RBD抗体水平显著增加。在分别用一剂或两剂RBD加强免疫的小鼠产生干扰素γ的CD4和CD8细胞中，也观察到PepMix™或RBD诱导的增殖率显著更高。ChAdOx1-S疫苗在增强特异性免疫方面效率较低可能是由于预先存在的抗载体免疫，这是由在小鼠和人类中均发现的抗腺病毒抗体水平升高所诱导的。综上所述，这些结果表明避免在对腺病毒有免疫和记忆的个体中反复使用相同腺病毒载体的重要性。这也说明了ChAdOx1腺病毒载体疫苗相对于重组蛋白疫苗的劣势，重组蛋白疫苗在疫苗加强免疫方案中可不受限制地使用。关键点：• ChAdOx1腺病毒疫苗（AZD1222）在增强抗SARS-CoV-2免疫方面可能无效 • 重组RBD蛋白疫苗在增强小鼠抗SARS-CoV-2免疫方面有效 • rRBD-德尔塔疫苗引发的抗体在小鼠中持续长达3个月。
