Publications by authors named "Ruth A Purcell"
Introduction: Substantial population-level variation in vaccine-specific antibody responses has been observed following global coronavirus disease 2019 (COVID-19) vaccination efforts. Beyond the influence of clinical and demographic features, immunogenetic variation is suggested to underlie divergent serological responses following COVID-19 vaccination of distinct populations.
Methods: Immunoglobulin G1 (IgG1) allotypic markers (G1m) for 121 COVID-19 vaccinated healthy adults were genotyped via Sanger sequencing.
Repeated mRNA COVID-19 vaccination increases spike-specific immunoglobulin G4 (IgG4) titers. Here, we characterized the influence of increased IgG4 titers on a range of Fc-mediated responses. Elevated spike-specific IgG4 reduced binding to FcγRIIIa and decreased antibody-dependent cellular cytotoxicity.
View Article and Find Full Text PDFEffect of Bacille Calmette-Guérin vaccination on immune responses to SARS-CoV-2 and COVID-19 vaccination.
Clin Transl Immunology
January 2025
Objectives: Bacille Calmette-Guérin (BCG) vaccination has off-target effects on disease risk for unrelated infections and immune responses to vaccines. This study aimed to determine the immunomodulatory effects of BCG vaccination on immune responses to vaccines against SARS-CoV-2.
Methods: Blood samples, from a subset of 275 SARS-CoV-2-naïve healthcare workers randomised to BCG vaccination (BCG group) or no BCG vaccination (Control group) in the BRACE trial, were collected before and 28 days after the primary course (two doses) of ChAdOx1-S (Oxford-AstraZeneca) or BNT162b2 (Pfizer-BioNTech) vaccination.
Article Synopsis
- The IGHG gene cluster encodes for different subclasses of immunoglobulin G (IgG) and is known for its high polymorphism, leading to various allotypes in humans.
- IGHG1 and IGHG3 are the most variable subclasses, with multiple allotypes, and recent studies have highlighted greater diversity in specific ethnic groups.
- The text outlines a detailed protocol for using PCR and Sanger sequencing to amplify IGHG gene segments and analyze SNPs linked to different allotypes of IgG1 and IgG3.
Immunoglobulin G genetic variation can confound assessment of antibody levels via altered binding to detection reagents.
Clin Transl Immunology
February 2024
Article Synopsis
- The study investigates how variations in immunoglobulin (Ig) allotypes, particularly of IgG1, can affect the accuracy of antibody detection in diverse genetic populations, focusing on two key haplotypes (G1m-1,3 and G1m1,17).
- Four commercial monoclonal antibodies were tested for their ability to recognize these haplotypes using assays, revealing that one antibody (4E3) showed a strong preference for binding to the G1m1,17 variant.
- The findings suggest that this bias in detection affects the interpretation of antibody responses in vaccinated and convalescent individuals, highlighting the importance of validating antibody clones against different Ig variants to improve accuracy in clinical assessments.
Article Synopsis
- Understanding mucosal antibody responses to SARS-CoV-2 is essential for creating longer-lasting immunity and countering new viral variants through profiling antibodies from different groups (vaccinated, uninfected; recovered, vaccinated; and breakthrough infections).
- Saliva from recovered vaccinees showed stronger antibody activity compared to uninfected vaccinees, indicating that prior infection enhances immune response, especially with IgA antibodies.
- Repeated mRNA vaccinations enhanced IgG responses, but preexisting immunity from vaccinations reduced effectiveness against breakthrough variants, highlighting the complexity of immune interactions and the potential for improved mucosal responses post-infection.
Mucosal antibody responses following Vaxzevria vaccination.
Immunol Cell Biol
November 2023
Mucosal antibodies play a key role in protection against breakthrough COVID-19 infections and emerging viral variants. Intramuscular adenovirus-based vaccination (Vaxzevria) only weakly induces nasal IgG and IgA responses, unless vaccinees have been previously infected. However, little is known about how Vaxzevria vaccination impacts the ability of mucosal antibodies to induce Fc responses, particularly against SARS-CoV-2 variants of concern (VoCs).
View Article and Find Full Text PDFPolyfunctional antibodies: a path towards precision vaccines for vulnerable populations.
Front Immunol
August 2023
Vaccine efficacy determined within the controlled environment of a clinical trial is usually substantially greater than real-world vaccine effectiveness. Typically, this results from reduced protection of immunologically vulnerable populations, such as children, elderly individuals and people with chronic comorbidities. Consequently, these high-risk groups are frequently recommended tailored immunisation schedules to boost responses.
View Article and Find Full Text PDFAntibody Fc-binding profiles and ACE2 affinity to SARS-CoV-2 RBD variants.
Med Microbiol Immunol
August 2023
Article Synopsis
- Emerging SARS-CoV-2 variants, particularly Omicron, pose significant public health challenges due to their mutations in the receptor-binding domain (RBD), a key region crucial for viral entry.
- A study examined these mutations' effects on immune response, finding reduced recognition and inhibition of ACE2 binding in response to Omicron and other variants, while retaining Fc antibody responses better than neutralization capabilities.
- Additionally, certain human ACE2 genetic variations were identified to either enhance or reduce binding to variant RBDs, highlighting potential implications for individual susceptibility to the virus.
High-risk groups, including Indigenous people, are at risk of severe COVID-19. Here we found that Australian First Nations peoples elicit effective immune responses to COVID-19 BNT162b2 vaccination, including neutralizing antibodies, receptor-binding domain (RBD) antibodies, SARS-CoV-2 spike-specific B cells, and CD4 and CD8 T cells. In First Nations participants, RBD IgG antibody titers were correlated with body mass index and negatively correlated with age.
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