Target intelligence / Profile preview

SARS-CoV-2 spike protein (expressed by Murine Pneumonia Virus vector) (SARS-CoV-2 S (MPV/S-2P))

Target
SARS-CoV-2 S (MPV/S-2P)
Molecular classification
Viral protein, Antigen, Surface glycoprotein, Type I fusion protein
01

Overview

The SARS-CoV-2 spike protein expressed by the MPV/S-2P vector is a prefusion-stabilized version of the viral surface glycoprotein, designed to elicit robust mucosal and systemic immune responses. The S-2P modification involves two proline substitutions (K986P and V987P) that lock the protein in its prefusion state, which is the most immunogenic form for inducing neutralizing antibodies (Kaiser et al., iScience, 2023). This specific construct is delivered via a live-attenuated Murine Pneumonia Virus (MPV) vector, which has a natural tropism for the respiratory tract but does not cause disease in humans (NIH/NIAID, 2024). By targeting the respiratory mucosa, the vaccine aims to provide superior protection against infection and transmission compared to traditional parenteral vaccines. Preclinical studies in non-human primates have demonstrated high levels of nasal IgA and serum IgG, as well as tissue-resident memory T-cells in the airways (Kaiser et al., Nat Commun, 2024). The vaccine is currently being evaluated in Phase 1 clinical trials as a next-generation booster to enhance immunity in previously vaccinated individuals (NCT06441968).

Other names
SARS-CoV-2 S-2PPrefusion-stabilized SARS-CoV-2 spike proteinMPV-vectored spike proteinMurine pneumonia virus-expressed spike proteinMPV/S-2P vaccine antigen
02

Mechanism of action

The MPV/S-2P vaccine functions by delivering a live-attenuated murine pneumonia virus vector that expresses the SARS-CoV-2 spike protein stabilized in its prefusion conformation (S-2P) directly to the respiratory epithelium. This localized expression induces a potent mucosal immune response, characterized by the production of secretory IgA and the recruitment of tissue-resident memory T-cells, alongside a systemic IgG response (Kaiser et al., Nat Commun, 2024). These immune components work together to neutralize the virus at the site of entry, potentially blocking both infection and transmission (NIH/NIAID, 2024).

03

Biological functions

Viral entryReceptor binding (ACE2)Immune response inductionMembrane fusionCellular attachment
04

Disease associations

InfectionCOVID-19
05

Safety considerations

Viral shedding of the MPV vector (NCT06441968)Local reactogenicity (e.g., nasal congestion, sore throat)Potential for mucosal inflammationTheoretical risk of recombination in immunocompromised hostsWaning of mucosal immunity over time
06

Interacting drugs

MPV/S-2P (investigational vaccine)
07

Biomarkers

Serum anti-S IgG antibody titers (Kaiser et al., iScience, 2023)Nasal wash anti-S IgA antibody titers (Kaiser et al., Nat Commun, 2024)S-specific CD4+ and CD8+ T-cell responses (Kaiser et al., Nat Commun, 2024)ACE2 binding inhibition activity (Kaiser et al., iScience, 2023)Viral vector shedding levels (NCT06441968)

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