Humoral Immunity across the SARS-CoV-2 Spike after Sputnik V (Gam-COVID-Vac) Vaccination

Abstract

Four years have passed since the World Health Organization (WHO) declared the COVID-19 pandemic due to SARS-CoV-2 on 11 March 2020. More than 770 million cases of COVID-19 and over 7 million deaths have been officially reported since then, althoughit is estimated that these numbers are considerably higher [1]. Nonetheless, SARS-CoV-2 vaccines have contributed to attenuate such a burden by promoting the development of effective immune responses, thus reducing the spread of the pandemic, the severity of the disease, hospitalizations and deaths [2]. SARS-CoV-2, which belongs to the family Coronaviridae, is an enveloped virus with a positive sense genome of around 30,000 nt. The genome codes for four structural proteins (nucleocapsid or N, spike or S, membrane or M and envelope or E), 15 nonstructural proteins and 8 accessory proteins [3]. The structural homotrimeric glycoprotein S has been used as the target for many of the vaccines developed [4,5]. This protein is composed of S1 and S2 subunits. The surface subunit S1 is composed of 672 amino acids and is organized into four domains: an N-terminal domain (NTD), a C-terminal domain (CTD, also known as the receptor-binding domain, RBD) and two subdomains (SD1 and SD2) [5]. The highly antigenic region known as the receptor-binding domain (RBD) mediates the interaction with the receptor angiotensin converting enzyme (ACE2) and the binding of the majority of neutralizing antibodies [6]. It is known that other epitopes outside the RBD, like the NTD, are also important in immunity and contribute to the antigenic profile of the S protein [7–9], but the effects of antibody recognition are not yet well characterized. The transmembrane subunit S2 is composed of 588 amino acids and contains a hydrophobic N-terminal fusion peptide (FP), two heptad repeats (HR1 and HR2), a transmembrane domain (TM) and a cytoplasmic tail (CT), the S2 subunit being the more conserved among all coronaviruses [10,11]. The S antigen was used as the immunogen in several vaccine constructs. Vaccine strategies included nonreplicating adenoviral vectors, nucleic acid (mRNA), whole inactivated viruses and protein subunit-based vaccines. The two-component adenovirus vector vaccine Gam-COVID-Vac (Sputnik-V) was the second-most distributed vaccine in Venezuela and was also employed in other Latin American countries [12,13]. Despite being distributed in at least 35 countries and having over 1.3 billion doses administered by March 2024 (according to ourworldindata.com, accessed on 13 March 2024), few studies are available on Sputnik-V efficacy and immunogenicity compared to other vaccines. In order to deepen the understanding of the effectiveness and immunogenicity of Sputnik-V, the aim of this study was to explore the antibody reactivity of individuals vaccinated with Sputnik-V towards different regions of S. Neutralizing antibody (NAb) activity was assessed and correlated with the reactivity of the antibodies to S over time.