Heterologous booster with a novel formulation containing glycosylated trimeric S protein is effective against Omicron

BOTTERO DANIELA; ERIKA RUDI; MARTIN AISPURO, PABLO; ZURITA, MARÍA EUGENIA; GAILLARD, MARÍA EMILIA; MARIA M GONZALEZ LOPEZ LEDESMA; MALITO JUAN; MATTHEW STUIBLE; AMBROSIS, NICOLÁS; YVES DUROCHER; GAMARNIK, ANDREA; ANDRÉS WIGDOROVITZ; DANIELA HOZBOR

Frontiers in Immunology

Frontiers

Año: 2023

1664-3224

In this study, we evaluated the efficacy of a heterologous three-dose vaccinationschedule against the Omicron BA.1 SARS-CoV-2 variant infection using a mouseintranasal challenge model. The vaccination schedules tested in this studyconsisted of a primary series of 2 doses covered by two commercial vaccines:an mRNA-based vaccine (mRNA1273) or a non-replicative vector-based vaccine(AZD1222/ChAdOx1, hereafter referred to as AZD1222). These were followed bya heterologous booster dose using one of the two vaccine candidates previouslydesigned by us: one containing the glycosylated and trimeric spike protein (S)from the ancestral virus (SW-Vac 2μg), and the other from the Delta variant ofSARS-CoV-2 (SD-Vac 2μg), both formulated with Alhydrogel as an adjuvant. Forcomparison purposes, homologous three-dose schedules of the commercialvaccines were used. The mRNA-based vaccine, whether used in heterologous orhomologous schedules, demonstrated the best performance, significantlyincreasing both humoral and cellular immune responses. In contrast, for theschedules that included the AZD1222 vaccine as the primary series, theheterologous schemes showed superior immunological outcomes comparedto the homologous 3-dose AZD1222 regimen. For these schemes no differenceswere observed in the immune response obtained when SW-Vac 2μg or SD-Vac2μg were used as a booster dose. Neutralizing antibody levels against OmicronBA.1 were low, especially for the schedules using AZD1222. However, a robustTh1 profile, known to be crucial for protection, was observed, particularly for theheterologous schemes that included AZD1222. All the tested schedules werecapable of inducing populations of CD4 T effector, memory, and follicular helperT lymphocytes. It is important to highlight that all the evaluated schedulesdemonstrated a satisfactory safety profile and induced multiple immunologicalmarkers of protection. Although the levels of these markers were differentamong the tested schedules, they appear to complement each other inconferring protection against intranasal challenge with Omicron BA.1 in K18-hACE2 mice. In summary, the results highlight the potential of using the S protein(either ancestral Wuhan or Delta variant)-based vaccine formulation asheterologous boosters in the management of COVID-19, particularly forcertain commercial vaccines currently in use.