新しいワクチンデザインは、インフルエンザに対する免疫を利用して、新興病原体に対するより迅速な防御を提供する(New vaccine design uses immunity against influenza to offer faster protection against emerging pathogens)

2024-01-17 カリフォルニア大学リバーサイド校(UCR)

<関連情報>

• https://news.ucr.edu/articles/2024/01/17/new-vaccine-design-uses-immunity-against-influenza-offer-faster-protection
• https://journals.asm.org/doi/10.1128/jvi.01571-23

既存のインフルエンザウイルス特異的免疫を利用することで、SARS-CoV-2に対する抗体応答が増加する Harnessing preexisting influenza virus-specific immunity increases antibody responses against SARS-CoV-2

Harrison Dulin, Ramya S. Barre, Duo Xu, Arrmund Neal, Edward Vizcarra, Jerald Chavez, Arzu Ulu, Myeon-Sik Yang, Siddiqur Rahman Khan, Keidy Wuang, Nikhil Bhakta, Chanvoraboth Chea, Emma H. Wilson, Luis Martinez-Sobrido, Rong Hai
Journal of Virology  Published:11 January 2024
DOI:https://doi.org/10.1128/jvi.01571-23

ABSTRACT

In pandemic scenarios involving novel human pathogenic viruses, it is highly desirable that vaccines induce strong neutralizing antibodies as quickly as possible. However, current vaccine strategies require multiple immunization doses to produce high titers of neutralizing antibodies and are poorly protective after a single vaccination. We therefore wished to design a vaccine candidate that would induce increased protective immune responses following the first vaccine dose. We hypothesized that antibodies against the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein could be increased by drawing upon immunity to a previous infection. We generated a fusion protein containing the influenza H1N1 PR8 virus nucleoprotein (NP) and the SARS-CoV-2 spike RBD. Mice with or without preexisting immunity to PR8 were then vaccinated with NP/RBD. We observed significantly increased SARS-CoV-2 neutralizing antibodies in mice with PR8 immunity compared to mice without preexisting PR8 immunity. Vaccination with NP/RBD protected mice from SARS-CoV-2-induced morbidity and mortality after a single dose. Additionally, we compared SARS-CoV-2 virus titers in the lungs and nasal turbinates 4 days post-challenge of mice vaccinated with NP/RBD. SARS-CoV-2 virus was detectable in the lungs and nasal turbinate of mice without preexisting PR8 immunity, while SARS-CoV-2 virus was completely undetectable in mice with preexisting PR8 immunity. We also found that CD4-positive T cells in mice with preexisting immunity to PR8 play an essential role in producing the increased antibody response against RBD. This vaccine strategy potentially can be modified to target other pathogens of concern and offers extra value in future pandemic scenarios.