Cold-adapted SARS-CoV-2 variants with different temperature sensitivity exhibit an attenuated phenotype and confer protective immunity

Single intranasal immunization with attenuated Wuhan-like SARS-CoV-2 provides highly effective cross-protection against Delta and Omicron VOCs

“…For the heterologous variants of the virus, Delta and especially Omicron, the neutralizing activity was predictably lower or absent, which is consistent with changes in the antigenic properties of the virus S-protein in the course of evolution and the results of previous studies (рис. 2В) (Aiano et al, 2023;Bowen et al, 2022;Dejnirattisai et al, 2022;Faizuloev et al, 2023;Wang et al, 2022).…”

“…D-D2 strain exhibited a temperature-sensitive (ts) phenotype (it did not reproduce at 39 C), which determined its reduced reproductive ability in the lungs of golden Syrian hamsters and, thus, an attenuative (att) phenotype. During intranasal immunization of hamsters, D-D2 strain exhibited high immunogenicity and protected against infection with homologous parental Dubrovka strain and the development of pneumonia (Faizuloev et al, 2023). The aim of the present study was to determine the immunization e cacy of attenuated Wuhan-like SARS-CoV-2 strain against heterologous challenge with strains belonging to the Delta variant and two sublineages of Omicron variant, BA.1.1 and BA.5.2.…”

“…The high potential of LAVs for COVID-19 prevention is supported by the observation that hybrid immunity (vaccination followed by a breakthrough infection) and SARS-CoV-2 reinfections reduce the risk of subsequent infections caused by the Omicron variant by 60% and 85%, respectively). Meanwhile, boosterization by breakthrough Omicron infection induces higher levels of memory B-cell and SARS-CoV-2-speci c T-cells, particularly against the Omicron variant, compared with booster immunization with inactivated or vector vaccines(Yu et al, 2023).Noteworthy, practically all developers of LAVs against COVID-19 achieve effective protection against challenges with the virulent strain by intranasal administration(Abdoli et al, 2022b;Faizuloev et al, 2023; Oral and intranasal administration of these vaccines provides not only induction of systemic cellular and humoral adaptive immune response but also the formation of mucosal (local) immunity, including secretion of speci c IgA-antibodies in the respiratory or intestinal mucosa. During intranasal immunization followed by infection with a virulent strain, speci c secretory IgA-antibodies neutralize the virus directly on the mucosa of the respiratory tract, which is the site of entry of infection, suppressing its adhesive ability and reducing the e ciency of transmission(Jacobson and Poland, 2002;Nian et al, 2022;Nouailles et al, 2023).…”

Single intranasal immunization with attenuated Wuhan-like SARS-CoV-2 provides highly effective cross-protection against Delta and Omicron variants of concern

“…Одни авторы для аттенуации вируса используют методы генной инженерии и обратной генетики, такие как сайт-направленный мутагенез и деоптимизация кодонов [9][10][11][12][13]. Другие используют традиционный подход, направленный на получение мутантов вируса путём длительного пассирования в культуре клеток в селективных условиях [14][15][16][17]. Независимо от методологии, применяемой для аттенуации вируса, важным вопросом, который определяет практическую значимость ЖАВ на настоящем этапе, является: сможет ли она обеспечить эффективную защиту не только при заражении «родительским» штаммом SARS-CoV-2, но и новыми, филогенетически отдалёнными вариантами вируса?…”

“…Штамм D-D2 проявлял температурочувствительный (ts) фенотип (не размножался при 39ºC), что определяло его сниженную репродуктивную способность в лёгких и аттенуационный (att) фенотип для золотистых сирийских хомячков. При интраназальной иммунизации хомячков штамм D-D2 проявлял высокую иммуногенность и защищал от заражения гомологичным родительским штаммом D и развития пневмонии [15].…”