In a recent study posted, researchers explored the protective systemic and mucosal immunity provided by a single dose of a live-attenuated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate.
Study
In the present study, researchers reported that a single-dose vaccination of a ∆3678 SARS-CoV-2 vaccine candidate protected mice from a SARS-CoV-2 challenge.
The team immunized K18-human angiotensin-converting enzyme 2 (hACE2) mice intranasally (i.n.) using 2×103 plaque-forming units (PFU) of the ∆3678 viruses. SARS-CoV-2 wildtype (WT)-infected or phosphate-buffered saline (PBS)-inoculated mice were employed as controls.
At 28 days post-vaccination (DPV), the team obtained blood, lung, spleen, and bronchoalveolar lavage (BAL) samples to assess immune responses induced by the virus. The protective effects of the ∆3678 mutant were examined by exposing the vaccinated mice to 104 PFU of the WT strain virus on 28 DPV.
The team also exposed the mice to the SARS-CoV-2 Omicron BA.5 subvariant to examine the protective effectiveness against a variant with lower antibody neutralization vulnerability than prior variants.
Findings
The study showed that all ∆3678 virus- or PBS-vaccinated animals survived 28 DPV and revealed neither clinical symptoms nor weight loss. However, 7.6% of the WT-infected animals inoculated with the same dose died within seven and 12 DPV. Also, almost one-third of the WT-infected mice displayed weight loss after seven DPV.
In the lung samples, WT and ∆3678 virus-infected mice had a Th1-prone immune reaction. CD4 + T cells obtained from the ∆3678-immunized mice had a higher or comparable proportion of interferon (IFN+) production than the WT virus cohort. This was suggested by the percentage and total cell number elevation; on the other hand, CD8+ IFNγ+ T cells revealed an improvement in percentage and total cell number.
Furthermore, WT and ∆3678 exposures stimulated high RBD-specific immunoglobulin (Ig)-A+ B cell responses, while the latter cohort displayed a 25% lower response. Similar proportions of SARS-CoV-2- specific IgG or IgA antibodies were identified in the BAL fluid samples of the ∆3678 and WT cohorts.
In the WT- and ∆3678-exposed mice, the team also noted Th1-prone immune responses in the spleen. CD4 + IFNγ+ T cells detected in the ∆3678-vaccinated mice revealed comparable cell numbers as those in the WT virus cohort with a decline in the percentage, while ∆3678 CD8 + T cells resulted in IFNγ levels similar to those in the WT virus concerning percentage and total cell number.
Additionally, WT and ∆3678 viruses elicited robust SARS-CoV-2-specific IgG and Th1-prone IgG2c in the serum samples, with no variations observed in antibody titers between the two cohorts.
The team also noted that mice with prior WT or ∆3678 virus inoculation survived the infection, while four out of nine PBS-vaccinated animals died between seven and nine days after the challenge.
Mice immunized with either strain reported no weight loss post-challenge, while naïve mice reported a loss of up to 20% of body weight by day seven post-challenge.
Mice with prior WT or ∆3678 virus inoculation revealed no detectable virus in their trachea or lung samples on days two and four and remarkably reduced viral loads within nasal washes at two days post-challenge.
Interestingly, none of the ∆3678-vaccinated mice reported detectable viruses in the trachea or lung samples two days post-challenge, while the naïve mice revealed viral loads of more than 106 PFU/g lung tissue.
Therefore, ∆3678 mutant vaccination provided equivalent protective effectiveness as the WT virus against future WT virus or variant exposure in mice.
Conclusion
The study findings showed that the ∆3678 SARS-CoV-2 vaccine highly protected K18-hACE2 mice. A single-dose vaccination with ∆3678 protected from WT and variant challenge by inducing SARS-CoV-2-specific systemic and mucosal humoral and cell-mediated immune responses.
The study also showed that mucosal administration of the live-attenuated vaccine promoted the development and functional activation of pulmonary cells. Therefore, the team believes that the ∆3678 viruses can be an effective candidate for future vaccinations, leading to improved and/or robust immunity in the respiratory tracts.
Source:
https://www.news-medical.net/news/20230420/Protective-mucosal-and-systemic-immunity-provided-by-a-single-dose-novel-live-attenuated-intranasal-SARS-CoV-2-vaccine-candidate.aspx