Since the first vaccine was developed against smallpox at the end of the 18th century, vaccines have become much more sophisticated and capable of eradicating previously deadly diseases. To date, over 25 diseases can be prevented by vaccines, which amounts of over 2.5 million deaths each year.
Despite these advancements, there is a growing need to utilize novel technologies to develop effective vaccines against major infectious diseases like human immunodeficiency virus (HIV) and malaria, as well as emerging infectious pathogens1.
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Introduction
Proteomics, which is the large-scale identification, quantification, localization, and characterization of cellular proteins, peptides, and post-translational modifications (PTMs), is a powerful tool that has been widely utilized for vaccine development.
Although liquid chromatography-mass spectrometry (LC-MS/MS) remains the most widely used technology for proteomic studies, other proteomic methods include microcapillary chromatography, spectral-counting, and stable isotope labeling by amino acids in cell culture (SILAC), to name a few.1
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What is Antibody Proteomics?
Antibody proteomics utilizes antibodies to explore both the proteome, as well as the structure and function of proteins within cells. Some of the different techniques that utilize antibodies for protein profiling include immunohistochemistry of tissue microarrays (TMAs), pathway analysis using reverse phase protein arrays (RPPAs), and serum-based diagnostic assays using antibody arrays.2
Antibody proteomics is widely used in vaccine research to investigate immune responses and identify proteins that are crucial for the identification of effective vaccine targets. Measuring vaccine-specific antibody levels through methods like enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition (HAI) assays is also crucial for determine the extent to which vaccines provide protection against target pathogens.1
Next Generation Vaccine Development with Proteomics
Applications of Proteomic Data in Vaccine Design
Immune Response Profiling
Proteomic vaccine studies often begin with examining the entire pathogen proteome and how the host immune system responds to infection. Historically, Western blot analysis using antibodies isolated from the serum of infected individuals was performed, following which proteins that interact with these antibodies in the blot are purified or digested for mass spectrometry analysis.1
Several studies have also isolated broadly neutralizing mAbs from previously infected individuals to determine their potential efficacy as a vaccine or prophylactic therapy. Previously, researchers identified a novel HIV-specific mAb 35O22, which has the potential to be used for prophylactic treatment for HIV.
Epitope Mapping
Previously, studies on Dengue virus vaccines have isolated B-cells from infected individuals that were found to produce strongly neutralizing antibodies against the virus. Thereafter, reactive B-cells were fused to myeloma cells to form hybridoma cells capable of releasing human monoclonal antibodies (mAbs) for epitope mapping and characterization.1
By examining the epitope composition of these antibodies, researchers can devise more effective vaccine candidates capable of inducing a similarly strong antibody response following immunization.
Case Studies and Examples
Previously, researchers printed the entire proteome of the vaccinia virus on microarray chips, after which serum from vaccinated individuals was applied to the chip to evaluate vaccine efficacy.
Antibodies presented within the serum sample bound to proteins on the chip were detected through a fluorescent signal that could be measured for quantification.1 When applied to patient samples, the researchers found that over 50% of serum antibodies were specific to non-envelope proteins.
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COVID-19 Vaccine Development
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19), continues to rapidly mutate. This has undermined the efficacy of previous COVID-19 vaccines and necessitated improvements to ensure their efficacy against novel viral variants. Nevertheless, researchers have failed to identify a single definitive biomarker capable of predicting the effectiveness of vaccines prior to immunization.
In a recent Protein & Cell study, researchers isolated peripheral blood mononuclear cells (PBMCs) from the serum of individuals who received CoronaVac for proteomic profiling to assess immune responses to vaccination. To this end, 38 proteins were differentially expressed between seropositive and seronegative individuals, whereas 33 proteins were dysregulated between baseline and one month following vaccination.3
Learn How to Interpret Proteomic Data
Future of Vaccine Research with Proteomic Data
Personalized Vaccines
In addition to utilizing proteomic methods to evaluate vaccine efficacy following immunization, researchers have also proposed the use of these approaches for predicting vaccine response by measuring biomarker levels prior to vaccination.1
In a pandemic setting, identifying individuals who may respond worse to certain vaccine candidates can allow for a more personalized approach to treating these patients, such as increased booster dose recommendations.
Rapid Pathogen Response
Traditional vaccine research often involves isolating and culturing pathogens, which can be expensive and time-consuming. In emergency situations, such as the COVID-19 pandemic, it is crucial to rapidly identify vaccine targets for emerging diseases to accelerate vaccine development.
Subtract proteomics involves comparing the proteomes of pathogens and hosts to identify proteins that are unique to the pathogens by ‘subtracting’ host-specific proteins from pathogen-specific proteins.4
Likewise, reverse vaccinology predicts protein-based vaccine candidates by analyzing the entire proteome of a pathogen and predicting which antigenic proteins could be used as novel vaccine targets. Recently, researchers have combined these methodologies to design innovative drugs and vaccines that target Gram-negative bacteria.
Conclusions
Recent advancements in proteomics have provided crucial insights into the development of vaccines and how these essential therapeutics induce immune responses to protect the public against a wide range of potentially lethal infectious diseases.
Aside from SARS-CoV-2, the World Health Organization (WHO) predicts that at least one new or previously dormant pathogen will emerge each year, thus emphasizing the crucial need for highly effective approaches that can be used to develop new vaccines or improve older vaccines.
‘’A combination of standardized immune serologic assays with the high-throughput transcriptomic, proteomic, and metabolomic measurements will provide the opportunity to predict immunological protection from vaccines.1”
References
- Galasse, A. C., & Link, A. J. (2015). Proteomic contributions to our understanding of vaccine and immune responses. Proteomics - Clinical Application. doi:10.1002/prca.201500054.
- Brennan, D. J., O’Connor, D. P., Rexhepaj, E., et al. (2010). Antibody-based proteomics: fast tracking molecular diagnostics in oncology. Nature Reviews Cancer 10; 605-617. doi:10.1038/nrc2902.
- Wang, Y., Zhu, Q., Sun, R., et al. (2023). Longitudinal proteomic investigation of COVID-19 vaccination. Protein & Cell 14(9); 668-682. doi:10.1093/procel/pwad004.
- Rahman, S., Chiou, C., Ahmad, S., et al. (2024). Subtractive Proteomics and Reverse-Vaccinology Approaches for Novel Drug Target Identification and Chimeric Vaccine Development against Bartonella henselae Strain Houstin-1. Bioengineering 11(5). doi:10/3390/bioengineering11050505.
Further Reading
The Role of Chemical Proteomics in Understanding Small Molecule-Protein Interactions