Researchers at Duke University, USA, are looking into the possibility of a combined influenza and coronavirus disease 2019 (COVID-19) vaccine that could be used to simultaneously protect against annual flu strains and the SARS-CoV-2. Preclinical results showed the vaccine protected mice from both SARS-CoV-2 and the flu. The vaccine could be a cost-effective measure in preventing influenza and coronavirus infections in countries that cannot afford expensive vaccine production. The researchers crafted a recombinant influenza A virus (IAV) genetic platform that allows the influenza virus to act as a vector packaging the SARS-CoV-2 . The goal of the seasonal combination vaccine is to target both influenza viruses and SARS-CoV-2. To test the vaccine’s effectiveness, they primed naive mice with either a wild-type strain or the combination vaccine. After three weeks, the animals were given an intramuscular booster shot of the inactivated vaccine or a control shot. The researchers collected blood samples two weeks after the booster to evaluate antibody activity.
High serum IgG levels were observed in vaccinated mice when blood samples were exposed to either the IAV hemagglutinin (HA) protein or the SARS-CoV-2 receptor-binding domain (RBD) protein. There was also no difference between IgG reactivity between both vaccine groups — even when there was less of the IAV HA protein in the vaccine. High antibody binding activity was associated with high neutralizing activity against the H1N1 IAV. The serum samples from vaccinated mice displayed stronger antibody reactivity against the SARS-CoV-2 receptor binding domain than the mice given the wild-type IAV vaccine. In addition, mice given the combination vaccine showed more neutralizing activity than those given the wild-type IAV vaccine group. Thus, the combination viral IAV/SARS CoV-2 vaccine is immunogenic and elicits a potentially protective humoral response against SARS-CoV-2. This additional antigenicity comes at no apparent cost for IAV directed immune responses, validating the platform concept of a combination viral particle-based vaccine.
The researchers looked at how the vaccine fares up against lethal viral doses — enough that would produce severe disease. They infected C57BL/6 mice and gave them the vaccine or a control. Results showed the mice in the control group rapidly lost weight and died. However, mice that received the wild-type IAV and the recombinant IAV/SARS-CoV-2 vaccine did not experience weight loss and did not succumb to infection. The experiment was repeated with transgenic mice that expressed the human SARS-CoV-2 receptor — increasing susceptibility for severe disease from the wildtype SARS-CoV-2 strain. Two weeks after receiving a booster shot, they were given an intranasal lethal dose of SARS-CoV-2. Mice vaccinated with the wild-type IAV experienced weight loss and death. In contrast, the mice with the combination vaccine were protected from infection. The researchers suggest the lack of infection in mice with the combination vaccine is likely due to the production of neutralizing antibodies.
An indipendent research team has developed a promising new anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate that utilizes nanotechnology and shows robust, long-lived immunity in mouse models. According to this new study, the vaccine enhanced the recruitment of APCs (antigen-presenting cells), increased spike-specific T lymphocytes, with a bias towards Th1 responses, IFN-γ and TNFα as the dominant cytokines, a more robust SARS-CoV-2 spike-specific recall response and presented broad protection against other coronavirus strains. The researchers have performed a thorough study of the vaccine-evoked innate and adaptive immune responses in mice against SARS-CoV-2. The molecular platform is ferritin, a naturally occurring, ubiquitous, iron-carrying protein that self-oligomerizes into a 24-unit spherical particle. Currently, it is currently evaluated as a vaccine platform for influenza in two phase 1 clinical trials with two further trials in the recruitment phase for Epstein Barr virus and Influenza H10 strain.
In this study, the researchers showed for the first time the effect of adjuvant design on antigen-presenting cell (APC) recruitment to the draining lymph nodes (dLNs) and its impact on a SARS-CoV-2 vaccine platform. They genetically linked the modified and stabilized prefusion-spike protein of the Wuhan-Hu-1 strain of SARS-CoV-2, to form a ferritin-fusion recombinant protein, which naturally forms a nanoparticle (SpFN). They then formulated it with either of the two distinct adjuvants used in this study: 1) an Army Liposome Formulation (ALFQ) and Aluminum Hydroxide gel (Alhydrogel®; AH). They observed robust and sustained recruitment and activation of classical and non-classical APCs in SpFN+ALFQ. The APC response to SpFN+ALFQ was characterized by conventional type 1 and type 2 dendritic cells, with upregulated costimulatory molecules necessary for T cells engagement and differentiation in contrast to SpFN+AH preparation. Intriguingly, they observed that this was associated with a potent TH1-biased cellular response and highly functional spike-specific memory T cells.
This study also presented a detailed cytokine profiling. The researchers noted that, strikingly, vaccination with SpFN+ALFQ resulted in spike-specific CD8+ T lymphocytes that established a memory pool. It is likely that this technology will be encountered in future vaccines, it is not yet known whether among the recalls of current anti-COVID vaccines or applied to other viruses. The fact that preliminary data indicate that the vaccine elicits a memory response of T lymphocytes gives hope that future immunity does not need to be renewed every 6 months or every year. A possibility yet to be tested.
- edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Maus M et al. bioRxiv 2021 May 3; 442425v1.
Carmen JM et al. bioRxiv 2021 Apr 28; 441763v1.
Maeda DNLF et al. PNAS USA 2021 May; 118(8).
Dott. Gianfrancesco Cormaci
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