A Universal Influenza Nanovaccine for “Mixing Vessel” Hosts Confers Potential Ability to Block Cross‐Species Transmission

Abstract

Influenza A virus (IAV), a deadly zoonotic pathogen, poses a tremendous threat and burden to global health systems. Pigs act as “mixing vessel” hosts to support and generate new pandemic viruses. Preventing the spread of IAV in pigs effectively can delay or even block cross‐species transmission. Universal vaccines based on the highly conserved ectodomain of influenza matrix protein 2 (M2e) have been widely reported, but have not been applied due to inadequate protection. Porcine circovirus type 2 (PCV2) causes immunosuppression and promotes swine influenza virus (SIV) infection. Here, M2e is inserted into capsid protein of PCV2 without burying the neutralizing epitopes and self‐assembles to form a bivalent nanovaccine. Inoculation with the nanovaccine induces robust M2e‐ and PCV2‐specific immune responses. The nanovaccine confers protection against lethal challenges of IAV from different species in mice, and significantly reduces SIV titers in pigs' respiratory tract and blocks SIV transmission. These results indicate that the nanovaccine is an economical and promising PCV2 and universal IAV bivalent vaccine, and it will synergistically and powerfully offer potential ability to block IAV cross‐species reassortment and transmission.

New Advances in Nanomaterial‐Based Antiviral Strategies

“…A bivalent nanovaccine was developed by inserting M2e into the capsid protein of porcine circovirus type 2 (PCV2), and it induced strong PCV2 and M2e‐specific immune responses and conferred protection against the infection of different IAV subtypes. [ 98 ] To increase the number of M2e copies in a vaccine, an intranasal nanovaccine was developed by displaying 3‐sequential repeats of M2e (3M2e) on the self‐assembling recombinant human heavy chain ferritin cage to form NPs. This nanovaccine induced strong M2e specific humoral, cellular, and mucosal immune responses without any adjuvants.…”

Development of vaccine formulations: past, present, and future

“…Although the seasonal flu vaccine is updated annually according to the epidemic prediction and influenza surveillance data, if it mismatched with the circulating strains, the vaccines will be ineffective. Ding et al prepared universal vaccines based on the highly conserved ectodomain of influenza matrix protein 2 (M2e) that were further inserted into capsid protein of porcine circovirus type 2 (PCV2) [ 79 ]. This nanovaccine induced high levels of M2e‐ and PCV2‐specific immune responses and protected mice from a lethal challenge of swine, human, and influenza A virus.…”

Nanovaccines against Animal Pathogens: The Latest Findings

“…However, it confers protection against influenza A challenge and blocks influenza transmission. Thus, this type of bivalent nanovaccine has the potential to act as a universal vaccine against influenza A virus and block its reassortment and cross-species transmission [ 151 , 152 ]. Chimeric VLP-based nanovaccines against rabies and FMDV co-expressing a novel fusion rabies glycoprotein have been recently investigated.…”