Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models

Corleis, Björn; Hoffmann, Donata; Rauch, Susanne; Fricke, Charlie; Roth, Nicole; Gergen, Janina; Kovacikova, Kristina; Schlottau, Kore; Halwe, Nico Joel; Ulrich, Lisa K.; Schön, Jacob; Wernike, Kerstin; Widera, Marek; Ciesek, Sandra; Mueller, Stefan O.; Mettenleiter, Thomas C.; Maione, Domenico; Petsch, Benjamin; Beer, Martin; Dorhoi, Anca

doi:10.1038/s41467-023-36110-1

Cited by 17 publications

(6 citation statements)

References 42 publications

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“…The bivalent vaccine induced more balanced serum IgG, IgA and neutralizing responses against ancestral and several Omicron strains in mice and hamsters. These results are consistent with studies showing that intramuscularly delivered bivalent SARS-CoV-2 mRNA vaccine boosters elicit antibody responses with greater breadth in humans and in animal models [41][42][43][44][45][46] and confer greater protection than monovalent boosters targeting the ancestral strain. Bivalent ChAd vaccine delivered i.n.…”

Section: Discussionsupporting

confidence: 90%

Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection

Ying,

Darling,

Desai

et al. 2024

Nat Immunol

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A nasally delivered chimpanzee adenoviral-vectored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine (ChAd-SARS-CoV-2-S) is currently used in India (iNCOVACC). Here, we update this vaccine by creating ChAd-SARS-CoV-2-BA.5-S, which encodes a prefusion-stabilized BA.5 spike protein. Whereas serum neutralizing antibody responses induced by monovalent or bivalent adenoviral vaccines were poor against the antigenically distant XBB.1.5 strain and insufficient to protect in passive transfer experiments, mucosal antibody and cross-reactive memory T cell responses were robust, and protection was evident against WA1/2020 D614G and Omicron variants BQ.1.1 and XBB.1.5 in mice and hamsters. However, depletion of memory CD8+ T cells before XBB.1.5 challenge resulted in loss of protection against upper and lower respiratory tract infection. Thus, nasally delivered vaccines stimulate mucosal immunity against emerging SARS-CoV-2 strains, and cross-reactive memory CD8+ T cells mediate protection against lung infection by antigenically distant strains in the setting of low serum levels of cross-reactive neutralizing antibodies.

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Section: Discussionsupporting

confidence: 90%

Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection

Ying,

Darling,

Desai

et al. 2024

Nat Immunol

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“…To further improve vaccine efficacy with regard to broader-protective and rapidly protective immunizations, several approaches have been undertaken. For mRNA vaccines, formulation and dosages have been optimized to result in a stronger activation of immune responses to improve the protective efficacy [ 49 , 50 , 51 , 52 , 53 , 54 ]. Several other approaches evaluated the effect of heterologous prime-boost regimens for the activation of broader-reactive and more robust immune responses [ 55 , 56 , 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Clever,

Limpinsel,

Meyer zu Natrup

et al. 2024

Viruses

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The sudden emergence of SARS-CoV-2 demonstrates the need for new vaccines that rapidly protect in the case of an emergency. In this study, we developed a recombinant MVA vaccine co-expressing SARS-CoV-2 prefusion-stabilized spike protein (ST) and SARS-CoV-2 nucleoprotein (N, MVA-SARS-2-ST/N) as an approach to further improve vaccine-induced immunogenicity and efficacy. Single MVA-SARS-2-ST/N vaccination in K18-hACE2 mice induced robust protection against lethal respiratory SARS-CoV-2 challenge infection 28 days later. The protective outcome of MVA-SARS-2-ST/N vaccination correlated with the activation of SARS-CoV-2-neutralizing antibodies (nABs) and substantial amounts of SARS-CoV-2-specific T cells especially in the lung of MVA-SARS-2-ST/N-vaccinated mice. Emergency vaccination with MVA-SARS-2-ST/N just 2 days before lethal SARS-CoV-2 challenge infection resulted in a delayed onset of clinical disease outcome in these mice and increased titers of nAB or SARS-CoV-2-specific T cells in the spleen and lung. These data highlight the potential of a multivalent COVID-19 vaccine co-expressing S- and N-protein, which further contributes to the development of rapidly protective vaccination strategies against emerging pathogens.

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“…On the contrary, some studies show boosting with variant-matched bivalent vaccines expands both cross-reactive and type-specific clones, and neutralizing antibodies are produced from each clone against the variant spike protein 27 . The studies indicate that boosting with bivalent vaccines are feasible approach for extending the coverage of vaccines for emerging and co-circulating SARS-CoV-2 variants 28 , 29 . Continued monitoring of neutralization and real-world vaccine effectiveness data are needed to set a preference policy between updated SARS-CoV-2 monovalent and bivalent vaccine boosters.…”

Section: Discussionmentioning

confidence: 99%

Omicron-specific and bivalent omicron-containing vaccine candidates elicit potent virus neutralisation in the animal model

Abdoli,

Jamshidi,

Taqavian

et al. 2024

Sci Rep

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Omicron variant (B.1.1.529) is able to escape from naturally acquired and vaccine-induced immunity, which mandates updating the current COVID-19 vaccines. Here, we investigated and compared the neutralising antibody induction of the ancestral variant-based BIV1-CovIran vaccine, the Omicron variant-based BIV1-CovIran Plus vaccine, and the novel bivalent vaccine candidate, BBIV1-CovIran, against the Omicron and ancestral Wuhan variants on the rat model. After inactivating the viral particles, the viruses were purified and formulated. Bivalent vaccines were a composition of 2.5 µg (5 µg total) or 5 µg (10 µg total) doses of each ansectral-based and Omicron-based monovalent vaccine. Subsequently, the potency of the monovalent and bivalent vaccines was investigated using the virus neutralisation test (VNT). The group that received three doses of the Omicron-specific vaccine demonstrated neutralisation activity against the Omicron variant with a geometric mean titer of 337.8. However, three doses of the Wuhan variant-specific vaccine could neutralise the Omicron variant at a maximum of 1/32 serum dilution. The neutralisation activity of the Omicron-specific vaccine, when administered as the booster dose after two doses of the Wuhan variant-specific vaccine, was 100% against the Omicron variant and the Wuhan variant at 1/64 and 1/128 serum dilution, respectively. Three doses of 5 µg bivalent vaccine could effectively neutralise both variants at the minimum of 1/128 serum dilution. The 10 µg bivalent vaccine at three doses showed even higher neutralisation titers: the geometric mean of 388 (95% CI 242.2–621.7) against Omicron and 445.7 (95% CI 303.3–655.0) against Wuhan. It is shown that the candidate bivalent and Omicron-specific vaccines could elicit a potent immune response against both Wuhan-Hu-1 and Omicron BA.1 variants.

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Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models

Cited by 17 publications

References 42 publications

Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection

Mucosal vaccine-induced cross-reactive CD8+ T cells protect against SARS-CoV-2 XBB.1.5 respiratory tract infection

Single MVA-SARS-2-ST/N Vaccination Rapidly Protects K18-hACE2 Mice against a Lethal SARS-CoV-2 Challenge Infection

Omicron-specific and bivalent omicron-containing vaccine candidates elicit potent virus neutralisation in the animal model

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