Future Challenges for Vaccinologists

Abstract

Vaccination is one of the cheapest health-care interventions that have saved more lives than any other drugs or therapies. Due to successful immunization programs we rarely hear about some of the common diseases of the early twentieth century including small pox and polio. Vaccination programs have also helped to increase food production notably poultry, cattle, and milk production due to lower incidence of infectious diseases in farm animals. Though vaccination programs have eradicated several diseases and increased the quality of life there are several diseases that have no effective vaccines. Currently there are no vaccines for cancer, neurodegenerative diseases, autoimmune diseases, as well as infectious diseases like tuberculosis, AIDS, and parasitic diseases including malaria. Abuse of antibiotics has resulted in the generation of several antibiotic-resistant bacterial strains; hence there is a need to develop novel vaccines for antibiotic-resistant microorganisms. Changes in climate is another concern for vaccinologists. Climate change could lead to generation of new strains of infectious microorganisms that would require development of novel vaccines. Use of conventional vaccination strategies to develop vaccines has severe limitations; hence innovative strategies are essential in the development of novel and effective vaccines.

Differential Antibody Recognition by Novel SARS-CoV-2 and SARS-CoV Spike Protein Receptor Binding Domains: Mechanistic Insights and Implications for the Design of Diagnostics and Therapeutics

“…This is particularly true for the conformational epitope at the N-and Cterminal region of SARS-CoV-2 RBD: the interacting region spans a large part of a well-defined betasheet subdomain ( Table 1, 2 and Figure 2). It is tempting to suggest that the expression of such subdomain in isolation could give rise to a highly immunoreactive molecule [19][20][21] .…”

“…Simply speaking, the termini of the linear segments making up the conformational epitopes could be aptly bridged with a number of Gly residues sufficient to approximate the distance in the experimental structure ( Table 3). Antibodies raised against these molecules, which recapitulate the main determinants of immunoreactivity of the full protein, could have useful applications in a therapeutic setting [19][20][21] . Furthermore, information on potentially specific SARS-CoV-2 spike RBD-specific epitopes can guide the synthesis of mimics of the epitope sequences in the form of peptides for use in diagnostic settings.…”

Targeting Difficult Protein-Protein Interactions with Plain and General Computational Approaches

“…In terms of vaccine development, reactive protein antigens can be exploited in formulations aimed to elicit protective responses against successive pathogenic challenges. Even if vaccines have traditionally suffered from slow routine studies, sometimes providing viable products well after the peak in the epidemics, the advent of ‘Reverse Vaccinology’ (RV) has revolutionized the field, introducing a whole new strategy of antigen selection [ 38 , 39 , 40 , 41 ]. Starting from the full genome analysis of a pathogen or from the analysis of multiple pathogens of a certain family, RV antigen candidates that show key properties required for vaccine development (e.g., cell-surface exposure, ability to interact with/elicit Abs, protein stability, possibility to produce the protein antigens in recombinant form) are selected.…”

The answer lies in the energy: how simple atomistic molecular dynamics simulations may hold the key to epitope prediction on the fully glycosylated SARS-CoV-2 spike protein

“…This detailed dynamic and structural knowledge can set the stage for understanding the molecular bases of S protein recognition by the host's immune system, providing information on which physicochemical determinants are required to elicit functional antibodies. Such understanding can then be exploited to design and engineer improved antigens based on S, for instance by identifying antigenic domains that can be expressed in isolation or short sequences (epitopes) that can be mimicked by synthetic peptides [15][16][17][18][19][20] : this would be a crucial first step in the selection and optimization of candidate vaccines and therapeutic antibodies, as well as in the development of serological diagnostic tools.…”