In the research on pathogenic bacteria, identifying the key factors for bacterial entry into cells and preventing bacteria or bacterial toxins from entering cells have become the research directions for nanobody (Nb) - based treatment of bacterial infections. For example, nanobodies can bind to the c - Met interaction site on the internalin B (InlB) of Listeria monocytogenes, competitively inhibiting bacterial invasion and preventing fetal infection. For gastrointestinal bacteria, nanobodies can be administered orally, bind to pathogenic bacteria in the extreme pH environment of the gastrointestinal tract, and neutralize bacterial infections [1].
Campylobacter is one of the common food - borne pathogenic bacteria in meat and meat products. Consumption of contaminated meat products can cause symptoms such as fever, severe diarrhea, and vomiting in humans. Nanobodies can specifically target the outer membrane proteins of Campylobacter jejuni and Campylobacter coli in broilers, blocking bacterial transmission [2].
Shigella is the pathogenic bacterium causing human bacillary dysentery, mainly transmitted through food. Barta et al. developed a set of nanobodies that can target and recognize different epitopes in IpaD on the tip complex of Shigella, and their heterodimers can reduce the hemolytic activity of Shigella by 80% [3].
In the treatment of sudden influenza, nanobodies can not only neutralize the virus or inhibit viral replication but also prevent influenza viruses from entering the nucleus by constructing anti - nucleoprotein nanobodies, thereby achieving the goal of treating influenza viruses. ALX - 0171, developed by Ablynx, is an inhalable nanobody used for the treatment of respiratory syncytial virus (RSV) infection and has currently entered the clinical research stage [4].
Human Immunodeficiency Virus (HIV) mainly attacks human T cells and damages the immune system, resulting in immunosuppression and eventually leading to Acquired Immunodeficiency Syndrome (AIDS). Studies by Robin A et al. have shown that bivalent and trivalent nanobodies can recognize the gp120 and gp41 epitopes on the envelope glycoprotein, significantly enhancing the neutralizing ability against HIV - 1. In addition, CXCR4 is a major co - receptor for HIV entry into host cells. Nanobodies targeting specific epitopes of CXCR4 can effectively inhibit HIV while avoiding interference with the normal physiological functions of CXCR4 [5].
In the treatment of parasitic infections, researchers have combined the modified apolipoprotein L - I with a nanobody targeting the conserved epitope of the surface glycoprotein of trypanosomes to obtain a fusion protein, which can induce trypanosome killing. In addition to fusion proteins, nanobody vesicles can also be constructed to encapsulate drugs and target the affected area for disease treatment. Arias et al. reported a nanovesicle conjugated with a nanobody targeting Trypanosoma brucei. In vitro pharmacodynamic experiments showed that the IC50 value of pentamidine encapsulated in these nanobody vesicles was 7 times lower than that of pentamidine alone [6].
In the research on the treatment of the aforementioned diseases, traditional drugs may have problems such as strong drug resistance and significant toxic and side effects. For instance, artemisinin - based drugs used for malaria treatment all have issues like short half - life and poor solubility. In contrast, nanobodies have high water solubility, are not prone to aggregation, and their extremely low immunogenicity allows them to avoid rejection by the body's immune system and reduce drug resistance. Meanwhile, nanobodies can target pathogens more precisely, reducing damage to normal cells. The half - life of nanobodies can also be extended through methods such as pegylation, conjugation or fusion with albumin, or fusion with Fc fragments.
Nanobodies are currently the smallest functional single - domain antibodies known to bind stably to antigens, with advantages such as low immunogenicity, strong targeted binding ability, and high water solubility. As a new type of antibody, nanobodies show promising application prospects in the prevention, diagnosis, and treatment of infectious diseases caused by viruses, bacteria, parasites, and other pathogens. We look forward to more surprises that nanobodies will bring to the cause of human health in the future.
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