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Cellular nanoparticles (CNPs), which refer to nanoparticles coated with natural cell membranes, are promising for neutralizing pathological agents. Here, we use CNPs as a medical countermeasure against the infection of SARS-CoV-2 variants in an animal model. CNPs comprise polymeric cores coated with the plasma membranes of human macrophages. The resulting nanoparticles (MΦ-NPs) act as host cell decoys to intercept SARS-CoV-2 and block its cellular entry, thus inhibiting subsequent viral infection. Our findings indicate that MΦ-NPs bind to the spike proteins of SARS-CoV-2 variants in a dose-dependent manner and inhibit the infectivity of live viruses. In hamsters infected with SARS-CoV-2 variants, MΦ-NPs significantly reduce the viral burden in the lungs, demonstrating their effectiveness in inhibiting viral infectivity in vivo. Furthermore, MΦ-NPs are primarily taken up by alveolar macrophages without inducing noticeable adverse effects. Given the crucial role of macrophages in viral infections, MΦ-NPs present a promising approach to combating emerging viral threats.

Cell membrane-based nanovaccines have demonstrated attractive features due to their inherently multiantigenic nature and ability to be formulated with adjuvants. Here, we report on cellular nanodiscs fabricated from cancer cell membranes and incorporated with a lipid-based adjuvant for antitumor vaccination. The cellular nanodiscs, with their small size and discoidal shape, are readily taken up by antigen-presenting cells and drain efficiently to the lymph nodes. Due to its highly immunostimulatory properties, the nanodisc vaccine effectively stimulates the immune system and promotes tumor-specific immunity. Using a murine colorectal cancer model, strong control of tumor growth is achieved in both prophylactic and therapeutic settings, particularly in combination with checkpoint blockades. Considerable therapeutic efficacy is also observed in treating a weakly immunogenic metastatic melanoma model. This work presents a new paradigm for the design of multiantigenic nanovaccines that can effectively activate antitumor immune responses and may be applicable to a wide range of cancers.

Acinetobacter baumannii is a leading cause of antibiotic-resistant nosocomial infections with high mortality rates, yet there is currently no clinically approved vaccine formulation. During the onset of A. baumannii infection, neutrophils are the primary responders and play a major role in resisting the pathogen. Here, we design a biomimetic nanotoxoid for antivirulence vaccination by using neutrophil membrane-coated nanoparticles to safely capture secreted A. baumannii factors. Vaccination with the nanotoxoid formulation rapidly mobilizes innate immune cells and promotes pathogen-specific adaptive immunity. In murine models of pneumonia, septicemia, and superficial wound infection, immunization with the nanovaccine offers significant protection, improving survival and reducing signs of acute inflammation. Lower bacterial burdens are observed in vaccinated animals regardless of the infection route. Altogether, neutrophil nanotoxoids represent an effective platform for eliciting multivalent immunity to protect against multidrug-resistant A. baumannii in a wide range of disease conditions.