Review VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants Wasim A. Prates-Syed 1,2,† , Lorena C. S. Chaves 3,† , Karin P. Crema 1,2 , Larissa Vuitika 1 , Aline Lira 1,2 , Nelson Côrtes 1,2 , Victor Kersten 1 , Francisco E. G. Guimarães 4 , Mohammad Sadraeian 4,5 , Fernando L. Barroso da Silva 6,7 , Otávio Cabral-Marques 1,8,9 , José A. M. Barbuto 1,10 , Momtchilo Russo 1 , Niels O. S. Câmara 1 and Gustavo Cabral-Miranda 1,2, *   Citation: Prates-Syed, W.A.; Chaves, L.C.S.; Crema, K.P.; Vuitika, L.; Lira, A.; Côrtes, N.; Kersten, V.; Guimarães, F.E.G.; Sadraeian, M.; Barroso da Silva, F.L.; et al. VLP-Based COVID-19 Vaccines: An Adaptable Technology against the Threat of New Variants. Vaccines 2021, 9, 1409. https://doi.org/10.3390/ vaccines9121409 Academic Editor: Vasso Apostolopoulos Received: 7 October 2021 Accepted: 20 November 2021 Published: 30 November 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affil- iations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1 Department of Immunology, Institute of Biomedical Sciences, University of São Paulo (ICB/USP), São Paulo 05508000, SP, Brazil; wasim.syed@usp.br (W.A.P.-S.); Karincrema@usp.br (K.P.C.); vuitika@usp.br (L.V.); aline.llira@usp.br (A.L.); nelson.cortes@usp.br (N.C.); vkersten@biof.ufrj.br (V.K.); otavio.cmarques@usp.br (O.C.-M.); jbarbuto@icb.usp.br (J.A.M.B.); momrusso@usp.br (M.R.); niels@icb.usp.br (N.O.S.C.) 2 Institute of Research and Education in Child Health (PENSI), São Paulo 01228200, SP, Brazil 3 Department of Microbiology and Immunology, School of Medicine, Emory University, Claudia Nance Rollins Building, Atlanta, GA 30329, USA; lorenachaves@emory.edu 4 São Carlos Institute of Physics, IFSC-USP, São Carlos 13566590, SP, Brazil; guimarae@ifsc.usp.br (F.E.G.G.); msadraeian@usp.br (M.S.) 5 Institute for Biomedical Materials & Devices (IBMD), Faculty of Science, University of Technology, Sydney, NSW 2007, Australia 6 Department of Biomolecular Sciences, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto 14040903, SP, Brazil; flbarroso@usp.br 7 Department of Chemical and Biomolecular Engeneering, North Carolina State University, Raleigh, NC 27695, USA 8 Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo 05508000, SP, Brazil 9 Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Children’s Medical Center, Tehran 1419733151, Iran 10 Laboratory of Medical Investigation in Pathogenesis and Targeted Therapy in Onco-Immuno-Hematology (LIM-31), Department of Hematology, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo 0124690, SP, Brazil * Correspondence: gcabral.miranda@usp.br † These authors have equally contributed. Abstract: Virus-like particles (VLPs) are a versatile, safe, and highly immunogenic vaccine platform. Recently, there are developmental vaccines targeting SARS-CoV-2, the causative agent of COVID-19. The COVID-19 pandemic affected humanity worldwide, bringing out incomputable human and financial losses. The race for better, more efficacious vaccines is happening almost simultaneously as the virus increasingly produces variants of concern (VOCs). The VOCs Alpha, Beta, Gamma, and Delta share common mutations mainly in the spike receptor-binding domain (RBD), demonstrat- ing convergent evolution, associated with increased transmissibility and immune evasion. Thus, the identification and understanding of these mutations is crucial for the production of new, op- timized vaccines. The use of a very flexible vaccine platform in COVID-19 vaccine development is an important feature that cannot be ignored. Incorporating the spike protein and its variations into VLP vaccines is a desirable strategy as the morphology and size of VLPs allows for better presentation of several different antigens. Furthermore, VLPs elicit robust humoral and cellular immune responses, which are safe, and have been studied not only against SARS-CoV-2 but against other coronaviruses as well. Here, we describe the recent advances and improvements in vaccine development using VLP technology. Keywords: virus-like particles; vaccines; COVID-19; SARS-CoV-2 Vaccines 2021, 9, 1409. https://doi.org/10.3390/vaccines9121409 https://www.mdpi.com/journal/vaccines