A biepitope, adjuvant-free, self-assembled influenza nanovaccine provides cross-protection against H3N2 and H1N1 viruses in mice

Abstract

Currently, the incorporation of multiple epitopes into vaccines is more desirable than the incorporation of a single antigen for universal influenza vaccine development. However, epitopes induce poor immune responses. Although the use of adjuvants can overcome this obstacle, it may raise new problems. Effective antigen delivery vehicles that can function as both antigen carriers and intrinsic adjuvants are highly desired for vaccine development. Here, we report a biepitope nanovaccine that provides complete protection in mice against H3N2 virus as well as partial protection against H1N1 virus. This vaccine (3MCD-f) consists of two conserved epitopes (matrix protein 2 ectodomain (M2e) and CDhelix), and these epitopes were presented on the surface of ferritin in a sequential tandem format. Subcutaneous immunization with 3MCD-f in the absence of adjuvant induces robust humoral and cellular immune responses. These results provide a proof of concept for the 3MCD-f nanovaccine that might be an ideal candidate for future influenza pandemics.

Self-assembled multiepitope nanovaccine based on NoV P particles induces effective and lasting protection against H3N2 influenza virus

“…The HMN-PP nanovaccine induced a higher titer of H16-specific antibodies than H16-KLH or H16-MAP4 using the Freund adjuvant [19], illustrating that epitopes can be combined with nanotechnology to enhance immunogenicity. Notably, M2e-PP induced high levels of nonneutralizing antibodies to engage in ADCC responses and protected mice from lethal H3N2 challenge, which was comparable to the results of the ferritin [51,52], CotB [53], and BP26 [54] nanoplatforms. In addition to neutralizing antibodies, nonneutralizing antibodies that can mediate ADCC also play an important role in protection from infection upon viral challenge [55,56].…”

Mechanism Exploration of Amyloid-β-42 Disaggregation by Single-Chain Variable Fragments of Alzheimer’s Disease Therapeutic Antibodies

“…In the folded state, Trp is usually buried in the hydrophobic nucleus of the protein and exposed to the surface during unfolding. This phenomenon leads to changes in emission intensity and the emission peak wavelength of sample fluorescence, which appears as an inflection point in the unfolded profile and is termed inflection temperature (Ti) [30,31]. The Ti ( • C) was 75.3, 62.5, 65.5, and 66.2 for BSA, scFv-C, scFv-S, and scFv-12B4, respectively.…”

Self-assembled ferritin nanoparticles displaying PcrV and OprI as an adjuvant-free Pseudomonas aeruginosa vaccine

“…3MCD-ferritin is also a nanoparticle carrying M2e and CD helix. Subcutaneous immunization with adjuvant-free 3MCD-ferritin induced Th1 and Th2 immune responses and provided complete protection against the H3N2 virus ( 26 ). In our study, without any adjuvant, the level of immune response induced by rePO-FN was as high as that induced by rePO formulated with Al(OH) 3 .…”

“…Traditionally, aluminum adjuvants facilitate the induction of a Th2-based immune response ( 26 , 27 ). However, recent findings indicate that it can also induce a Th17 response.…”