Immunization route-mediated differences in long-term maturation of humoral immune response induced by adenovirus vector-based COVID-19 vaccine Sputnik V in nonhuman primates

Amir I. Tukhvatulin^1*Ilya V. Gordeychuk^2,3Alina S. Dzharullaeva¹Inna V. Dolzhikova¹Ekaterina O. Bayurova²Anna V. Kovyrshina¹Alla S. Zhitkevich²Daria V. Avdoshina²Stanislav A. Gulyaev²Tatiana V. Gulyaeva²Andrey V. Moroz²Viktoria V. Kuchina²Ilya D. Zorkov¹Anna A. Iliukhina¹Artem Y. Shelkov¹Alina S. Erokhova¹Dmitry V. Shcheblyakov¹Olga V. Zubkova¹Aydar A. Ishmukhametov²Denis Y. Logunov^1,3Alexander L. Gintsburg^1,3

• ¹National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F. Gamaleya of the Ministry of Health of the Russian Federation, Moscow, Russia
• ²Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences (Institute of Poliomyelitis), Moscow, Russia
• ³I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia

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 post-vaccination humoral immune response in nonhuman primates induced by adenoviral COVID-19 vaccine administered by the intramuscular and intranasal routes commonly used in clinical practice.