Self-assembling protein nanoparticles in the design of vaccines

By J. López-Sagaseta, E. Malito, Rino Rappuoli, Matthew J. Bottomley. 2015

326 citations recorded by the source corpus.

For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.

Subfields: Ecology, Immunology, Radiology, Nuclear Medicine and Imaging

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Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “In contrast, self-assembling or particulate protein immunogens are a clinically validated vaccine modality with a proven track record of safety and efficacy in humans (López-Sagaseta et al., 2015).”
Induction of Potent Neutralizing Antibody Responses by a Designed Protein Nanoparticle Vaccine for Respiratory Syncytial Virus (2019, background): “The correlation we observed between increased antigen density and immunogenicity agrees with previous work using other multivalent antigen presentation platforms (for review, see Frietze et al., 2016; López-Sagaseta et al., 2015) and supports the notion that efficient cross-linking of BCRs by high-d”
Title: Mosaic nanoparticles elicit cross-reactive immune responses to zoonotic coronaviruses in mice (2020, unknown): “Multivalent display of antigen enhances B-cell responses and can provide longer-lasting immunity than monovalent antigens (27, 28), thus protein-based vaccine candidates often .”
Tailored design of protein nanoparticle scaffolds for multivalent presentation of viral glycoprotein antigens (2020, background): “These studies have illustrated the advantages of using self-assembling proteins as scaffolds for antigen presentation (López-Sagaseta et al., 2016; Kanekiyo et al., 2019), including enhanced immunogenicity and seamless integration of antigen and scaffold through genetic fusion.”
Therapeutic Nanoparticles and Their Targeted Delivery Applications (2020, background): “Virus-like particles (VLP), a type of protein nanoparticles, are defined as nano-carrier systems, which have a morphologically similar, virus-isolated structure but do not include the viral genetic material [29,30].”