A Heterologous V-01 or Variant-Matched Bivalent V-01D-351 Booster following Primary Series of Inactivated Vaccine Enhances the Neutralizing Capacity against SARS-CoV-2 Delta and Omicron Strains

Abstract

Immune escape of emerging SARS-CoV-2 variants of concern (VOCs) and waning immunity over time following the primary series suggest the importance and necessity of booster shot of COVID-19 vaccines. With the aim to preliminarily evaluate the potential of heterologous boosting, we conducted two pilot studies to evaluate the safety and immunogenicity of the V-01 or a bivalent V-01D-351 (targeting Delta and Beta strain) booster after 5–7 months of the primary series of inactivated COVID-9 vaccine (ICV). A total of 77 participants were enrolled, with 20 participants in the V-01D-351 booster study, and 27, 30 participants in the age stratified participants of V-01 booster study. The safety results showed that V-01 or V-01D-351 was safe and well-tolerated as a heterologous booster shot, with overall adverse reactions predominantly being absent or mild in severity. The immunogenicity results showed that the heterologous prime–boost immunization with V-01 or bivalent V-01D-351 booster induced stronger humoral immune response as compared with the homologous booster with ICV. In particular, V-01D-351 booster showed the highest pseudovirus neutralizing antibody titers against prototype SARS-CoV-2, Delta and Omicron BA.1 strains at day 14 post boosting, with GMTs 22.7, 18.3, 14.3 times higher than ICV booster, 6.2, 6.1, 3.8 times higher than V-01 booster (10 μg), and 5.2, 3.8, 3.5 times higher than V-01 booster (25 μg), respectively. The heterologous V-01 booster also achieved a favorable safety and immunogenicity profile in older participants. Our study has provided evidence for a flexible roll-out of heterologous boosters and referential approaches for variant-specific vaccine boosters, with rationally conserved but diversified epitopes relative to primary series, to build herd immunity against the ongoing pandemic.

Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant

“…These results are consistent with human serum data obtained after immunization with bivalent mRNA vaccines targeting B.1.351 16,17 or BA.1 14,18 . Increases in neutralizing antibody breadth with bivalent vaccine formulations or boosters also have been reported in the context of inactivated 25,26 and spike protein-based [27][28][29] SARS-CoV-2 vaccine candidates.…”

Safety and immunogenicity of a bivalent SARS-CoV-2 protein booster vaccine, SCTV01C, in adults previously vaccinated with mRNA vaccine: a randomized, double-blind, placebo-controlled phase 1/2 clinical trial

“…The WHO Technical Advisory Group on COVID-19 Vaccine Composition (TAG-CO-VAC) has recommended updating the composition of current COVID-19 vaccines when developing multivalent or broad-protective vaccines against SARS-CoV-2 current and future emerging variants. 9 Trials based on broad-spectrum anti-coronavirus vaccines using multivalent design, including mRNA-1273.211 (bivalent wild type and Beta variants, Moderna), 10 mRNA-1273.214 (bivalent wild type and omicron B.1.1.529 variants), 5 NVSI-06-08 (recombinant protein vaccine, three heterologous RBDs from the prototype, Beta and Kappa SARS-CoV-2 strain, Sinopharm) 11 and V-01D-351 (recombinant protein vaccine, bivalent from Beta and Delta, Livzon) 12 are in progress.…”

Structural and Computational Design of a SARS-2 Spike Antigen with Increased Receptor Binding Domain Exposure and Improved Immunogenicity

“…S-2P has previously been shown to have two distinct melting transitions (Tm1 and Tm2) with an increase in Tm1 being indicative of improved stability [38]. All three NTD + S2 designs (8,9,10) had Tm1 values greater than S-2P (Tm1 = 44 °C), with design 9 having the largest, yet modest, increase of 4.2 °C (Tm1 = 48 °C) (Table 1). Tm1 values for all four S2 domain designs (12, 13, 14, and 15) were comparable to S-2P.…”

“…However, the efficacies of these first-generation vaccines are diminished against newly circulating variants of concern (VoCs) such as Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (BA.1, BA.2, BA.4/5, XBB, and BQ.1.1), which evade neutralizing antibodies and/or cell mediated immunity due to mutations in the S protein [1][2][3][4][5][6][7][8]. Though booster vaccines have been developed to match S protein sequences of circulating variants [9][10][11][12], there is no guarantee that these updated vaccines will protect against future strains of the virus [7,8,[13][14][15]. Therefore, there is a need for the development of vaccine antigens which can elicit Abs that are more efficient in neutralizing future variants, thus providing broader and/or, longer lasting protection.…”