Other HNMs including AuNPs (two subcutaneous injections in guinea pigs) and nanodiamonds (three subcutaneous injections in Balb/C mice) were explored as carriers of viral proteins for immunization of swine transmissible gastroenteritis virus and H7N9 influenza, respectively, with good preliminary results.146,147 In these cases, the vaccine formulation relies on the adsorption of the viral antigen onto the surface of the nanoparticles. However, an effective vaccination depends on several factors. First of all, the size of the NPs plays a key role on the immune system. For instance, size-dependent vaccination efficacy has been reported in mice immunization against the foot-and-mouth disease virus (intraperitoneal and subcutaneous injection, every 7 days for 7 weeks) using AuNPs as antigen carriers. In this study, the most effective activity to stimulate the immune system was exerted by particles with a diameter in the range of 8 nm.148 Both smaller or bigger particles evidenced a drop-off of the immunization effect. This aspect cannot be ascribed to the antigen concentration, but must be associated only to the nanoparticle size; however, the mechanism of interaction remains unknown. The selected antigen plays also a crucial role in the preparation of wide spectrum vaccines. For instance, in the case of influenza, two major membrane glycoproteins, hemagglutinin and neuraminidase, are generally used as antigens. However, the antibodies produced by this vaccination strategy are selective to the dominant epitope which has a low effectiveness or is totally ineffective against other epitopes or other kinds of influenza viruses. M2 (a viral protein responsible for the budding and scission of the influenza virus) is commonly expressed in different types of influenza viruses with a high rate of conservation but with low antigenicity. It has been shown that AuNPs functionalized with M2e protein have a high immunization capacity in comparison to the antigen alone. Mice immunized with AuNPs (two intranasal injections), and then challenged, showed a survival rate higher than 90% to California-H1N1pdm, Victoria-H3N2, and Vietnam-H5N1 infections.149 This strategy shows that HNMs can be used to boost the immune response of low immunogenic molecules, providing a wide spectrum vaccination potential. Unfortunately, it has not been determined if the budding process in SARS-Cov-2 is mediated by viral proteins or via the host cell’s endosomal sorting complex, thus more research on the SARS-Cov-2 viral machinery is highly desirable.