The adaptive potential of North American subtype H7N2 avian influenza viruses to mammals

Introduction. H7 subtype avian influenza viruses causing severe epizootics among birds are phylogenetically different in the Eastern and Western hemispheres. Numerous human infections caused by these viruses in the Eastern hemisphere indicate that H7 viruses can overcome the interspecies barrier and pose a potential threat of a new pandemic.The H7N2 viruses with deletion of amino acids 221–228 (H3 numbering) in hemagglutinin (HA) had been circulating among poultry in the Western Hemisphere during 1996–2006, and had once again been detected in 2016 in an animal shelter, where they caused cat diseases. The objective of this study is to elucidate the mechanism of adaptation to mammals of North American H7N2 influenza viruses with deletion in HA. Materials and methods. The A/chicken/New Jersey/294598-12/2004 (H7N2) virus was adapted to mice by the lung passages. Complete genomes of original and mouse-adapted viruses were analyzed. The receptor specificity and thermostability of viruses, HA activation pH and virulence for mice were determined. Results. The non-pathogenic H7N2 avian influenza virus became pathogenic after 10 passages in mice. Amino acid substitutions occurred in five viral proteins: one in PB2 (E627K), NA (K127N), NEP (E14Q), four in HA and six in NS1. Mutations in HA slightly changed receptor specificity but increased the pH of HA activation by 0.4 units. The NS1 protein undergone the greatest changes in the positions (N73T, S114G, K118R, G171A, F214L and G224R), where amino acid polymorphisms were observed in the original virus, but only minor amino acid variants have been preserved in the mouse adapted variant. Conclusion. The results show that H7N2 viruses have the potential to adapt to mammals. The increase in virulence is most likely due to the adaptive E627K mutation in PB2 and possibly in HA

Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination

Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines

Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination

Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines

Functional Profiling of In Vitro Reactivated Memory B Cells Following Natural SARS-CoV-2 Infection and Gam-COVID-Vac Vaccination

Both SARS-CoV-2 infection and vaccination have previously been demonstrated to elicit robust, yet somewhat limited immunity against the evolving variants of SARS-CoV-2. Nevertheless, reports performing side-by-side comparison of immune responses following infection vs. vaccination have been relatively scarce. The aim of this study was to compare B-cell response to adenovirus-vectored vaccination in SARS-CoV-2-naive individuals with that observed in the COVID-19 convalescent patients six months after the first encounter with the viral antigens. We set out to use a single analytical platform and performed comprehensive analysis of serum levels of receptor binding domain (RBD)-specific and virus-neutralizing antibodies, frequencies of RBD-binding circulating memory B cells (MBCs), MBC-derived antibody-secreting cells, as well as RBD-specific and virus-neutralizing activity of MBC-derived antibodies after Gam-COVID-Vac (Sputnik V) vaccination and/or natural SARS-CoV-2 infection. Overall, natural immunity was superior to Gam-COVID-Vac vaccination. The levels of neutralizing MBC-derived antibodies in the convalescent patients turned out to be significantly higher than those found following vaccination. Our results suggest that after six months, SARS-CoV-2-specific MBC immunity is more robust in COVID-19 convalescent patients than in Gam-COVID-Vac recipients. Collectively, our data unambiguously indicate that natural immunity outperforms Gam-COVID-Vac-induced immunity six months following recovery/vaccination, which should inform healthcare and vaccination decisions

Functional Profiling of In Vitro Reactivated Memory B Cells Following Natural SARS-CoV-2 Infection and Gam-COVID-Vac Vaccination

Both SARS-CoV-2 infection and vaccination have previously been demonstrated to elicit robust, yet somewhat limited immunity against the evolving variants of SARS-CoV-2. Nevertheless, reports performing side-by-side comparison of immune responses following infection vs. vaccination have been relatively scarce. The aim of this study was to compare B-cell response to adenovirus-vectored vaccination in SARS-CoV-2-naive individuals with that observed in the COVID-19 convalescent patients six months after the first encounter with the viral antigens. We set out to use a single analytical platform and performed comprehensive analysis of serum levels of receptor binding domain (RBD)-specific and virus-neutralizing antibodies, frequencies of RBD-binding circulating memory B cells (MBCs), MBC-derived antibody-secreting cells, as well as RBD-specific and virus-neutralizing activity of MBC-derived antibodies after Gam-COVID-Vac (Sputnik V) vaccination and/or natural SARS-CoV-2 infection. Overall, natural immunity was superior to Gam-COVID-Vac vaccination. The levels of neutralizing MBC-derived antibodies in the convalescent patients turned out to be significantly higher than those found following vaccination. Our results suggest that after six months, SARS-CoV-2-specific MBC immunity is more robust in COVID-19 convalescent patients than in Gam-COVID-Vac recipients. Collectively, our data unambiguously indicate that natural immunity outperforms Gam-COVID-Vac-induced immunity six months following recovery/vaccination, which should inform healthcare and vaccination decisions