Beta Spike-Presenting SARS-CoV-2 Virus-Like Particle Vaccine Confers Broad Protection against Other VOCs in Mice DOI Open Access
Irfan Ullah, Kelly Symmes,

Kadiatou Keita

и другие.

Опубликована: Июнь 13, 2024

Vaccine antigens must present the correct conformation of viral fusion glycoproteins to elicit effective immune responses. Virus-like particles (VLPs) serve as promising vaccine platforms because they mimic membrane-embedded conformations on native viruses. Here, we employed SARS-CoV-2 VLPs (SMEN) presenting ancestral, Beta, or Omicron spikes identify variant that elicits potent and cross-protective responses in highly sensitive K18-hACE2 mouse model. A combined intranasal intramuscular administration regimen SMEN generated was predominantly mediated by antibodies with minor contributions from T cells. Immunization an ancestral spike resulted 100, 75, 0% protection against Delta Beta VOC-induced mortality, respectively, whereas most divergent provided only limited (50%, 0%, 25%) Delta, variants, respectively. By contrast, a offered 100% variants used this study. Thus, not overcame immunity produced other but also elicited diverse response. Our findings suggest leveraging protein can enhance immunity, potentially leading more comprehensive emerging variants.

Язык: Английский

Simian Immunodeficiency Virus-Based Virus-like Particles Are an Efficient Tool to Induce Persistent Anti-SARS-CoV-2 Spike Neutralizing Antibodies and Specific T Cells in Mice DOI Creative Commons
Alessandra Gallinaro, Chiara Falce, Maria Franca Pirillo

и другие.

Vaccines, Год журнала: 2025, Номер 13(3), С. 216 - 216

Опубликована: Фев. 21, 2025

Background/Objectives: Virus-like particles (VLPs) represent an attractive platform for delivering vaccine formulations, combining a high biosafety profile with potent immune-stimulatory ability. VLPs are non-infectious, non-replicating, self-assembling nanostructures that can be exploited to efficiently expose membrane-tethered glycoproteins such as the SARS-CoV-2 Spike (S) protein, main target of approved preventive vaccines. Here, we describe development and preclinical validation Simian Immunodeficiency Virus (SIV)-based GFP-labeled displaying S from B.1.617.2 (Delta) variant (VLP/S-Delta) inducing persistent anti-SARS-CoV-2 neutralizing antibodies (nAbs) S-specific T cell responses in mice. Methods: SIV-derived VLP/S-Delta were produced by co-transfecting plasmid expressing SIVGag-GFP, required VLP assembly quantification flow virometry, encoding Delta protein deleted cytoplasmic tail (CT), improve membrane binding, VSV.G-expressing plasmid, enhance uptake. Recovered titrated virometry characterized vitro transmission electron microscopy (TEM) confocal (CLSM). BALB/c mice immunized intramuscularly following prime–boost regimen, humoral cellular immune assessed. Results: pseudotyped CT-truncated S-Delta. After priming, elicited both specific anti-RBD IgGs anti-Delta nAbs significantly increased after boost maintained over time. The vaccination induced similar levels cross-nAbs against ancestral Wuhan-Hu-1 strain well Omicron BA.1, BA.2 BA.4/5 VoCs, albeit at lower levels. Moreover, immunization IFNγ-producing cells. Conclusions: These data suggest SIV-based appropriate delivery system elicitation efficient sustained immunity mice, paving way further improvements immunogen design quality breadth different viral glycoproteins.

Язык: Английский

Процитировано

0
Beta Spike-Presenting SARS-CoV-2 Virus-Like Particle Vaccine Confers Broad Protection against Other VOCs in Mice DOI Open Access
Irfan Ullah, Kelly Symmes,

Kadiatou Keita

и другие.

Опубликована: Июнь 13, 2024

Vaccine antigens must present the correct conformation of viral fusion glycoproteins to elicit effective immune responses. Virus-like particles (VLPs) serve as promising vaccine platforms because they mimic membrane-embedded conformations on native viruses. Here, we employed SARS-CoV-2 VLPs (SMEN) presenting ancestral, Beta, or Omicron spikes identify variant that elicits potent and cross-protective responses in highly sensitive K18-hACE2 mouse model. A combined intranasal intramuscular administration regimen SMEN generated was predominantly mediated by antibodies with minor contributions from T cells. Immunization an ancestral spike resulted 100, 75, 0% protection against Delta Beta VOC-induced mortality, respectively, whereas most divergent provided only limited (50%, 0%, 25%) Delta, variants, respectively. By contrast, a offered 100% variants used this study. Thus, not overcame immunity produced other but also elicited diverse response. Our findings suggest leveraging protein can enhance immunity, potentially leading more comprehensive emerging variants.

Язык: Английский

Процитировано

1