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Trimeric protein vaccine based on Beta variant elicits robust immune response against BA.4/5-included SARS-CoV-2
Cai He1, Li Chen1, Jingyun Yang1
1Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, China.
Abstract:
The current Coronavirus Disease 2019 (COVID-19) pandemic, induced by newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants, posed great threats to global public health security. There is an urgent need to design effective next‑generation vaccines against Omicron lineages. Here, we investigated the immunogenic capacity of the vaccine candidate based on the receptor binding domain (RBD). An RBDβ-HR self-assembled trimer vaccine including RBD of Beta variant (containing K417, E484 and N501) and heptad repeat (HR) subunits was developed using an insect cell expression platform. Sera obtained from immunized mice effectively blocked RBD-human angiotensin-converting enzyme 2 (hACE2) binding for different viral variants, showing robust inhibitory activity. In addition, RBDβ-HR/trimer vaccine durably exhibited high titers of specific binding antibodies and high levels of cross-protective neutralizing antibodies against newly emerging Omicron lineages, as well as other major variants including Alpha, Beta, and Delta. Consistently, the vaccine also promoted a broad and potent cellular immune response involving the participation of T follicular helper (Tfh) cells, germinal center (GC) B cells, activated T cells, effector memory T cells, and central memory T cells, which are critical facets of protective immunity. These results demonstrated that RBDβ-HR/trimer vaccine candidates provided an attractive next-generation vaccine strategy against Omicron variants in the global effort to halt the spread of SARS-CoV-2.
Insights
A novel receptor binding domain (RBD) trimer vaccine targeting SARS-CoV-2 Omicron variants demonstrated robust immunogenicity in mice. This vaccine candidate induced durable antibody and cellular immune responses, offering a promising strategy against emerging COVID-19 strains.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- The COVID-19 pandemic, driven by SARS-CoV-2 Omicron variants, necessitates advanced vaccine strategies.
- Existing vaccines face challenges against rapidly evolving viral lineages.
- The receptor binding domain (RBD) is a key target for neutralizing antibodies.
Purpose of the Study:
- To evaluate the immunogenic potential of a novel RBD-based trimer vaccine against SARS-CoV-2 Omicron variants.
- To assess the vaccine's ability to elicit neutralizing antibodies and cellular immune responses.
- To determine the cross-protective efficacy against various SARS-CoV-2 variants.
Main Methods:
- Development of an RBD-beta (RBDβ)-heptad repeat (HR) self-assembled trimer vaccine using an insect cell expression platform.
- Immunization of mice with the RBDβ-HR trimer vaccine.
- Assessment of sera for inhibition of RBD-human angiotensin-converting enzyme 2 (hACE2) binding.
- Measurement of antibody titers and neutralizing antibody levels against multiple SARS-CoV-2 variants.
- Analysis of cellular immune responses, including T follicular helper (Tfh) cells, germinal center (GC) B cells, and various T cell populations.
Main Results:
- Sera from immunized mice effectively blocked RBD-hACE2 binding across different viral variants.
- The RBDβ-HR/trimer vaccine induced durable high titers of specific binding antibodies.
- The vaccine elicited high levels of cross-protective neutralizing antibodies against Omicron lineages and other variants (Alpha, Beta, Delta).
- A broad and potent cellular immune response was observed, involving Tfh cells, GC B cells, and memory T cells.
Conclusions:
- The RBDβ-HR/trimer vaccine candidate demonstrates significant immunogenic capacity against SARS-CoV-2 Omicron variants.
- This vaccine strategy shows potential for broad cross-protection against major SARS-CoV-2 variants.
- The vaccine effectively stimulates key cellular immune components crucial for protective immunity, representing a promising next-generation vaccine approach.
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