Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

Tong, Dali; Zhang, Mei; Yu, Yang; Xia, Han; Tong, Haiyang; Zhang, Huajun; Zeng, Weihong; Liu, Muziying; Wu, Yan; Ma, Huan; Liu, Weiyong; Cai, Yuan; Yao, Yanfeng; Yao, Yichuan; Liu, Kunpeng; Shan, Shifang; Li, Yajuan; Gao, Ge; Guo, Weiwei; Peng, Yun; Chen, Shaohong; Rao, Juhong; Zhao, Jiaxuan; Min, Juan; Zhu, Qingjun; Zheng, Yanmin; Liu, Lianxin; Shan, Chao; Qiu, Zilong; Jin, Tengchuan; Chiu, Sandra; Yuan, Zhiming; Xue, Tian

doi:10.1093/procel/pwac020

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…Many types of vaccines have been developed to control the infection and spread of SARS-CoV-2, including vaccines based on messenger RNA (mRNA) 3 , viral vectors 4,5 , recombinant proteins 6 , and inactivated SARS-CoV-2 7 . Immunization with these vaccines showed a reduction in infection rates and post-infection mortality.…”

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confidence: 99%

“…To test the antibody level against different variants of SARS-CoV2, we collected the plasma of 41 infected patients (11 unvaccinated patients, 7 with 2-dose inactivated SARS-CoV2 vaccine, 13 with 3-dose inactivated SARS-CoV2 or recombinant protein vaccine and 10 with 4-dose inactivated SARS-CoV2 or recombinant protein vaccine) and 15 uninfected people, including 10 people received the latest boost (4 th dose) less than 3 months and 5 people received the latest boost more than 6 months. We then tested the antibody titer (IgG) in the plasma against the prototype, Omicron BA.5, BF.7, and XBB 1.5 variants using ELISA test 4 . Surprisingly, we found that the antibody level against Omicron BA.5, BF.7, and XBB 1.5 of the individuals has a high positive correlation with the antibody level against prototype SARS-CoV2 (Figure 1 F).…”

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confidence: 99%

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A survey and antibody test following the surge of SARS-CoV-2 Omicron infection in China

Yao

et al. 2023

Preprint

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The surge of SARS-CoV-2 Omicron infection in most Chinese residents at the end of 2022 provided a unique opportunity to understand how the immune system responds to the Omicron infection in a population with limited contact to prior SARS-CoV-2 variants. Moreover, whether the prototype SARS-CoV-2 booster vaccination could help induce the antibody against Omicron variants? Here, we tested the level of IgG, IgA, and IgM specific to the prototype SARS-CoV-2 spike RBD (Receptor Binding Domain) from the collected blood samples from 636 individuals. Sequential inoculation of different vaccines showed higher IgG levels after infection. As the antibody level against Omicron BA.5, BF.7, and XBB 1.5 of the individuals has highly positive correlation with the antibody level against prototype SARS-CoV2, the IgG level specific to the prototype SARS-CoV-2 spike RBD could also represent the IgG level against Omicron variants. Furthermore, the 4thbooster vaccination could induce a comparable antibody level against prototype, Omicron BA.5, BF.7, and XBB 1.5 variants in the patients with 2 or 3-dose vaccination and protect people from being infected. In conclusion, these data suggest that the prototype SARS-CoV-2 booster vaccination helps induce a high level of antibody against prototype, BA.5, BF.7, and XBB 1.5 variants after Omicron infection.

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A survey and antibody test following the surge of SARS-CoV-2 Omicron infection in China

Yao

et al. 2023

Preprint

Self Cite

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An AAV vaccine targeting the RBD of the SARS-CoV-2 S protein induces effective neutralizing antibody titers in mice and canines

Liu

Feng

et al. 2022

Vaccine

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The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in catastrophic damage worldwide. Accordingly, the development of powerful, safe, easily accessible vaccines with long-term effectiveness is understood as an urgently needed countermeasure against this ongoing pandemic. Guided by this strong promise of using AAVs, we here designed, optimized, and developed an AAV-based vaccines (including AAV-RBD(max), AAV-RBD(wt), AAV-2xRBD, and AAV-3xRBD) that elicit strong immune responses against the RBD domain of the SARS-CoV-2 S protein. These immunogenic responses have proven long-lived, with near peak levels for at least six months in mice. Notably, the sera immunized with AAV-3xRBD vaccine contains powerful neutralizing antibodies against the SARS-CoV-2 pseudovirus. Further evidence proven that potent specific antibodies could also be elicited in canines after vaccination with AAV-3xRBD vaccine.

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rAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose

Wiggins,

Winston,

Reeves

et al. 2024

J Virol

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Influenza remains a worldwide public health threat. Although seasonal influenza vaccines are currently the best means of preventing severe disease, the standard-of-care vaccines require frequent updating due to antigenic drift and can have low efficacy, particularly in vulnerable populations. Here, we demonstrate that a single administration of a recombinant adenovirus-associated virus (rAAV) vector expressing a computationally optimized broadly reactive antigen (COBRA)-derived influenza H1 hemagglutinin (HA) induces strongly neutralizing and broadly protective antibodies in naïve mice and ferrets with pre-existing influenza immunity. Following a lethal viral challenge, the rAAV-COBRA vaccine allowed for significantly reduced viral loads in the upper and lower respiratory tracts and complete protection from morbidity and mortality that lasted for at least 5 months post-vaccination. We observed no signs of antibody waning during this study. CpG motif enrichment of the antigen can act as an internal adjuvant to further enhance the immune responses to allow for lower vaccine dosages with the induction of unique interferon-producing CD4+ and CD8+ T cells specific to HA head and stem peptide sequences. Our studies highlight the utility of rAAV as an effective platform to improve seasonal influenza vaccines. IMPORTANCE Developing an improved seasonal influenza vaccine remains an ambitious goal of researchers and clinicians alike. With influenza routinely causing severe epidemics with the potential to rise to pandemic levels, it is critical to create an effective, broadly protective, and durable vaccine to improve public health worldwide. As a potential solution, we created a rAAV viral vector expressing a COBRA-optimized influenza hemagglutinin antigen with modestly enriched CpG motifs to evoke a robust and long-lasting immune response after a single intramuscular dose without needing boosts or adjuvants. Importantly, the rAAV vaccine boosted antibody breadth to future strains in ferrets with pre-existing influenza immunity. Together, our data support further investigation into the utility of viral vectors as a potential avenue to improve our seasonal influenza vaccines.

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Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques

Cited by 3 publications

References 25 publications

A survey and antibody test following the surge of SARS-CoV-2 Omicron infection in China

A survey and antibody test following the surge of SARS-CoV-2 Omicron infection in China

An AAV vaccine targeting the RBD of the SARS-CoV-2 S protein induces effective neutralizing antibody titers in mice and canines

rAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose

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