See the original article here: https://www.frontiersin.org/articles/10.3389/fimmu.2021.701501/full
Discussion
For the adequate design of COVID-19 vaccines, we must consider the selection of antigens, the proper selection of the platform for antigen production, adjuvants and other substances used during vaccine formulation. However, the success of the SARS-CoV-2 vaccines will also depend to a large extent on the production capacity to meet the volumes required by a global pandemic, an adequate distribution of doses, correct administration regimens, as well as appropriate use according to the type of vaccine, which could contribute to combat SARS-CoV-2 emerging variants.
Because the generation of new variants is aleatory, the longer the pandemic lasts, the higher the probability for the generation of new variants. Therefore, controlling rapidly the pandemic worldwide by a combination of a well-organized vaccination campaign coupled with strict sanitary measurements are key factors to prevent extending the pandemic for another year or even longer.
The S glycoprotein has been the main target for the development of vaccines against SARS-CoV-2 (4) and has been shown to be efficient enough to protect individuals who are vaccinated with this antigen or highly immunogenic regions of the same, such as the RBD (188). Companies such as Pfizzer & Biontech, AstraZeneca, Novavax, CanSino Biological, and Inovio Pharmaceuticals, have chosen to use the complete S glycoprotein, each following different strategies modifying the structural characteristics of the S glycoprotein, with the aim of improving its expression, recognition, stability or immunogenicity (67, 74, 78, 79, 150). Alternatively, other companies or academic institutions have chosen to use highly immunogenic regions within the S glycoprotein, such as the RBD. RBD-based vaccines may present modifications that improve their presentation, including the incorporation into VLPs (101), trimerization motifs (103), domain duplications (102) and even fusion carrier proteins (104). In addition, other types of vaccines such as those based on epitopes from the S glycoprotein are currently tested in animals models (112).
The wide variety of proposals approved and in clinical phases allows several options to design the best vaccination strategies against the SARS-CoV-2 (6). However, the emergence of new variants casts doubts on the effectiveness of the vaccines developed so far (174). It has been shown that some mutations present in new variants escape neutralization, particularly mutations found around the RBD (171–173). Given these mutations in the RBD, some vaccines have shown moderate neutralizing effects with variants such as B.1.351 and P.1 (150, 152, 158, 159). So far, only vaccines based on full-length S glycoprotein have been evaluated regarding their ability to neutralize new SARS-CoV-2 variants (182). It is imperative to evaluate the effectiveness of all vaccines against new variants if we intend to control the pandemic and prevent COVID-19 from becoming an endemic disease. Still, much like influenza, we cannot discard the possibility of having to generate new vaccines against emerging SARS-CoV-2 variants every year and implement frequent vaccination programs.
We consider that due to the emergence of new SARS-CoV-2 variants in countries with limited access to vaccines, the redesign SARS-CoV-2 vaccines based on these new variants is highly recommended.
We propose that the redesign of SARS-CoV-2 vaccines based on S glycoprotein, RBD or its epitopes should be considered for their proper use according to the geographic distribution of the SARS-CoV-2 variants. For example, epitope-based vaccines could have a lesser effect in countries with high prevalence of variants with immune escape, such as that observed with variants B.1.351 and P.1.
We should take full advantage of strategies such as genomic databases, structure prediction systems, and predictors of antigenic determinants in the design of vaccines against emerging variants (189), which may be useful assets to predict conformational and linear epitopes that can be recognized by B lymphocytes (190, 191). Most of the vaccines in use or in more advanced clinical trials utilize the complete SARS-CoV-2 virus, the full-length S glycoprotein, the RBD domain or RNA encoding the S glycoprotein (Tables 1 and 2).
Biomaterials are defined as substances of synthetic or natural origin, which can interact with living systems, in which they can perform therapeutic or diagnostic functions in order to improve the quality of life of individuals (192). The use of biomaterials in the development of vaccines against SARS-CoV-2 has been widely extended including: VLPs, DNA, RNA, liposomes, viral vectors, among others (Tables 1 and 2). However, the use of biomaterials in combination with peptides and predicted epitopes has not been sufficiently explored. There are biomaterials that form nano and microstructures which have been shown efficacy as antigen delivery systems, as enhancers of the immune response (adjuvant) and as antigen stabilizers (193, 194). Polymers and copolymers (195, 196), self-assembling proteins and self-assembling peptides (SAPNs and SAPs, respectively) (197, 198), microneedles (199), metallic nanoparticles (199, 200) and carbon nanomaterials (200). All of the previous mentioned biomaterials should be extensively explored in new generation of SARS-CoV-2 vaccines.
Conclusion
We must recognize that the design and development of efficient vaccines against SARS-CoV-2 is the best strategy to combat COVID-19, fortunately many of them have shown high efficiency. Nevertheless, the emergence of new variants can jeopardize the success achieved so far with vaccination. To reach total control of the COVID-19 pandemic, the combination of several strategies will be necessary, which include an adequate distribution of SARS-CoV-2 vaccines taking into consideration the geographical distribution of the variants, the re-designing or SARS-CoV-2 antigens as well as the use of other technological tools such as bioinformatics and the use of novel biomaterials.