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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background/Objectives: Since December 2019, the COVID-19 pandemic, driven by SARS-CoV-2, has caused ~690 million infections globally, manifesting with mild to severe symptoms, including pneumonia. After reduced activity, seasonal influenza re-emerged in winter 2022, creating a “twindemic” with SARS-CoV-2. Co-infections have been associated with higher risks, such as increased ventilator use and mortality, emphasizing the need for dual-target vaccines. This study investigates plant-based vaccines produced using a bacterium-like particle (BLP) system from Lactobacillus sakei to co-target SARS-CoV-2 and influenza. Methods: DNA fragments of the SARS-CoV-2 Omicron BA.1 variant spike (S) protein and H1N1 virus hemagglutinin (HA) ectodomain were synthesized and used to create recombinant constructs introduced into Agrobacterium. Protein expression was analyzed using Western blot and Bradford protein assays. Six-week-old K18-hACE2 mice were immunized with these antigens and challenged with influenza, SARS-CoV-2, or both to assess viral load and lung pathology at various times. Results: The SARS-CoV-2 S protein and influenza HA protein were successfully expressed in Nicotiana benthamiana and demonstrated strong binding to BLPs. In mouse models (BALB/c and K18-hACE2), these vaccines elicited potent humoral and cellular immune responses, with high neutralizing antibody titers and increased IFN-γ levels. Vaccinated mice demonstrated protection against viral challenges, reduced lung viral loads, and improved survival. In cases of co-infection, vaccinated mice showed rapid recovery and effective viral clearance, highlighting the potential of vaccines to combat simultaneous SARS-CoV-2 and influenza infections. Conclusions: Our findings highlight the potential of BLP-based multivalent vaccines for dual protection against major public health threats.

Details

Title
Development of Plant-Based Multivalent Vaccine Candidates for SARS-CoV-2 and Influenza Virus Using Inactivated Lactococcus
Author
Dong-Sook, Lee 1   VIAFID ORCID Logo  ; Banna, Hasanul 2 ; Kim, Heeyeon 1 ; Md Rezaul Islam Khan 3 ; Hai-Ping Diao 3 ; Shi-Jian, Song 3 ; Young-Eui, Kim 1 ; Kang, Haeji 1 ; Ryou, Jungsang 1 ; Joo-Yeon, Lee 4 ; Jang-Hoon, Choi 1 ; Hwang, Inhwan 3 ; Park, Sehee 1 

 Division of Acute Viral Disease, Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Cheongju 28159, Republic of Korea; [email protected] (D.-S.L.); [email protected] (H.K.); [email protected] (Y.-E.K.); [email protected] (H.K.); [email protected] (J.R.); [email protected] (J.-H.C.) 
 School of Interdisciplinary Bioscience and Bioengineering, Pohang University of Science and Technology (POSTECH), Pohang 37673, Republic of Korea; [email protected] 
 Department of Life Science, Pohang University of Science and Technology, Pohang 37673, Republic of Korea; [email protected] (M.R.I.K.); [email protected] (H.-P.D.); [email protected] (S.-J.S.) 
 Center for Emerging Virus Research, National Institute of Infectious Diseases, National Institute of Health, Cheongju 28159, Republic of Korea; [email protected] 
First page
254
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
2076393X
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3181826225
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.