Tukhvatulin Amir I, Gordeychuk Ilya V, Dzharullaeva Alina S, Dolzhikova Inna V, Bayurova Ekaterina O, Izhaeva Fatima M, Kovyrshina Anna V, Zhitkevich Alla S, Avdoshina Daria V, Gulyaev Stanislav A, Gulyaeva Tatiana V, Moroz Andrey V, Esmagambetov Ilias B, Zorkov Ilya D, Iliukhina Anna A, Shelkov Artem Y, Erokhova Alina S, Shcheblyakov Dmitry V, Zubkova Olga V, Ishmukhametov Aydar A, Logunov Denis Y, Gintsburg Alexander L
National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, Moscow, Russia.
Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, Russia.
Front Immunol. 2025 Sep 12;16:1634187. doi: 10.3389/fimmu.2025.1634187. eCollection 2025.
On the background of kaleidoscopic changes of SARS-CoV-2 circulating variants, constant presence of SARS-CoV-2 in the human population hampers the dissection of native long-term immunogenicity of COVID-19 vaccines.
For this purpose, we performed a more than two-year-long evaluation of parameters of the humoral immune response elicited by intramuscularly (IM) and intranasally (IN) delivered adenovirus vector-based Sputnik V vaccine in nonhuman primates (NHP, Common marmosets), which are naturally nonsusceptible for SARS-CoV-2 infection.
Although both immunization routes elicited prominent humoral immune responses in a short-term perspective, the long-term kinetics significantly differed between the IM and IN groups. While the titers of local and systemic antigen-specific antibodies (both IgA and IgG) nearly disappeared within two years upon IN vaccination, IM vaccination led to the highest IgG values in nasal swabs as well as IgA and IgG in serum specimens from NHPs by the end of observation period (day 764). Unlike IN vaccination, IM vaccination also resulted in a continuous long-term increase in serum maturation parameters such as antibody avidity, neutralization potency and breadth.
The present study provides valuable information about distinct features of the long-term postvaccination humoral immune response in nonhuman primates induced by adenoviral COVID-19 vaccine administered by the intramuscular and intranasal routes commonly used in clinical practice.
在严重急性呼吸综合征冠状病毒2（SARS-CoV-2）循环变体千变万化的背景下，SARS-CoV-2在人群中的持续存在阻碍了对新冠病毒疾病（COVID-19）疫苗天然长期免疫原性的剖析。
为此，我们对非人灵长类动物（NHP，普通狨猴）中通过肌肉注射（IM）和鼻内（IN）接种基于腺病毒载体的卫星五号疫苗引发的体液免疫反应参数进行了为期两年多的评估，这些动物对SARS-CoV-2感染天然不敏感。
尽管从短期来看，两种免疫途径均引发了显著的体液免疫反应，但IM组和IN组的长期动力学存在显著差异。鼻内接种后，局部和全身抗原特异性抗体（IgA和IgG）的滴度在两年内几乎消失，而在观察期结束时（第764天），肌肉注射疫苗导致NHP鼻拭子中的IgG值最高，血清标本中的IgA和IgG值也最高。与鼻内接种不同，肌肉注射疫苗还导致血清成熟参数如抗体亲和力、中和效力和广度持续长期增加。
本研究提供了关于临床实践中常用的肌肉注射和鼻内接种腺病毒COVID-19疫苗在非人灵长类动物中诱导的疫苗接种后长期体液免疫反应的独特特征的有价值信息。
