The roles of immuno-modulator treatment and echocardiographic screening in rheumatic fever and rheumatic heart disease control: research from Aotearoa, New Zealand.

This review summarises advances in research from Aotearoa, New Zealand (NZ) that have potential to reduce the inequitable distribution of acute rheumatic fever (ARF) and rheumatic heart disease (RHD). ARF incidence and RHD prevalence are unacceptably inequitable for Māori and Pacifica. Recent qualitative research has demonstrated mismatches between the lived experience of those with ARF/RHD and health service experience they encounter.

Decline of antibodies to major viral and bacterial respiratory pathogens during the COVID-19 pandemic.

Surges in infections caused by respiratory pathogens have been documented in multiple settings after relaxation of pandemic restrictions. Antibodies to major antigens from respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal adult cohort throughout the pandemic. This waning may have contributed to the pathogen-surges that followed.

Characterization of an IL-8 cleavage inhibition assay to determine the functionality of anti-SpyCEP antibodies in human sera.

Exposure to Group A Streptococcus leads to a broad spectrum of disease and sequelae, as the bacterium employs a wide range of virulence factors to facilitate colonization of the host, propagation and onward transmission, disrupting both innate and adaptive immune responses. The protease SpyCEP has a crucial role in contributing to bacterial immune evasion by impairing neutrophil recruitment and killing of bacteria through the cleavage of interleukin-8 (IL-8). Given this critical function, SpyCEP represents a key vaccine antigen and quantifying functional anti-SpyCEP antibodies represents not only an important marker of vaccine efficacy, but also a tool to dissect the natural immune response.

The SARS-CoV-2 neutralising antibody profile of New Zealand adults in 2023: Impact of vaccination and infection.

The successive dominance of SARS-CoV-2 omicron sublineages presents challenges for vaccination strategies with respect to the antigenic content of boosters. New Zealand's COVID-19 elimination strategy (2020-2021) ensured the major vaccination campaign (Pfizer-BioNTech BNT162b2) was completed pre-omicron in an infection-naive population, providing a unique setting to explore the impact of omicron infection waves on vaccine responses. This study compared neutralising antibodies (NAb) to eight SARS-CoV-2 omicron sublineages 28-days and 11-months after a third dose.

The Emergence and Impact of the M1 Lineage on Invasive Group A Streptococcus Disease in Aotearoa New Zealand.

M1 is associated with current surges in invasive infection globally, partly due to increased production of superantigen streptococcal pyrogenic exotoxin A. We show that M1 is now the dominant invasive 1 lineage in Aotearoa New Zealand and is genomically related to community infections, suggesting that measures that effectively prevent group A pharyngitis in children could reduce invasive disease.

Reduction in Acute Post-Streptococcal Glomerulonephritis Incidence in Counties Manukau, New Zealand, after the COVID-19 Pandemic.

The COVID-19 pandemic has altered the epidemiology of many common childhood infections, including Group A streptococcal (GAS) disease. Acute post-streptococcal glomerulonephritis (APSGN) is a nonsuppurative complication of GAS pharyngitis and pyoderma. It remains the most common cause of pediatric acute glomerulonephritis globally.

Development and characterization of a hemolysis inhibition assay to determine functionality of anti-Streptolysin O antibodies in human sera.

The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make the development of an effective vaccine a global health priority. Streptolysin O (SLO), is a key toxin in the complex pathogenesis of Strep A infection. Antibodies are elicited against SLO after natural exposure and represent a key target for vaccine-induced immunity.

A worldwide population of strains circulating among school-aged children in Auckland, New Zealand: a genomic epidemiology analysis.

Background: Acute rheumatic fever (ARF) is a serious post-infectious sequala of Group A (GAS, ). In New Zealand (NZ) ARF is a major cause of health inequity. This study describes the genomic analysis of GAS isolates associated with childhood skin and throat infections in Auckland NZ.

Naturally acquired functional antibody responses to group A differ between major strain types.

Group A (GAS) is a leading human pathogen for which there is no licensed vaccine. Infections are most common in young children and the elderly suggesting immunity accumulates with exposure until immune senescence in older age. Though protection has been postulated to be strain type specific, based on the M-protein (-type), the antigenic basis of population-level immunity remains poorly understood.

Robust immunogenicity of a third BNT162b2 vaccination against SARS-CoV-2 Omicron variant in a naïve New Zealand cohort.

The ability of a third dose of the Pfizer-BioNTech BNT162b2 SARS-CoV-2 vaccine to stimulate immune responses against subvariants, including Omicron BA.1, has not been assessed in New Zealand populations. Unlike many overseas populations, New Zealanders were largely infection naïve at the time they were boosted.

Identification of an immunodominant region on a group A T-antigen reveals temperature-dependent motion in pili.

Group A (GAS) is a globally important pathogen causing a broad range of human diseases. GAS pili are elongated proteins with a backbone comprised repeating T-antigen subunits, which extend from the cell surface and have important roles in adhesion and establishing infection. No GAS vaccines are currently available, but T-antigen-based candidates are in pre-clinical development.

Human antibody profiling technologies for autoimmune disease.

Autoimmune diseases are caused by the break-down in self-tolerance mechanisms and can result in the generation of autoantibodies specific to human antigens. Human autoantigen profiling technologies such as solid surface arrays and display technologies are powerful high-throughput technologies utilised to discover and map novel autoantigens associated with disease. This review compares human autoantigen profiling technologies including the application of these approaches in chronic and post-infectious autoimmune disease.

The effects of sugar in drinking water on Streptococcus pyogenes colonisation in a murine nasopharyngeal infection model.

The number of sugar-sweetened beverages consumed per day has been associated with an increased risk of acute rheumatic fever, an autoimmune disease triggered by superficial Streptococcus pyogenes infection. To explore if there could be a biological basis for this association, we used a mouse model of S. pyogenes nasopharyngeal colonisation combined with a dietary intervention.

Cytokine imbalance in acute rheumatic fever and rheumatic heart disease: Mechanisms and therapeutic implications.

Acute Rheumatic Fever (ARF) and Rheumatic Heart Disease (RHD) are autoimmune sequelae of Group A Streptococcus infection with significant global disease burden. The pathogenesis of these diseases is poorly understood, and no immune modulating therapies are available to stop progression from ARF to RHD. Cytokines and chemokines are immune signaling molecules critical to the development of autoimmune diseases.

Risk factors for acute rheumatic fever: A case-control study.

Background: Acute rheumatic fever (ARF) and rheumatic heart disease (RHD) remain an inequitable cause of avoidable suffering and early death in many countries, including among Indigenous Māori and Pacific populations in New Zealand. There is a lack of robust evidence on interventions to prevent ARF. This study aimed to identify modifiable risk factors, with the goal of producing evidence to support policies and programs to decrease rates of ARF.

Immunogenicity of BNT162b2 COVID-19 vaccine in New Zealand adults.

Background: There is very little known about SARS-CoV-2 vaccine immune responses in New Zealand populations at greatest risk for serious COVID-19 disease.

Methods: This prospective cohort study assessed immunogenicity in BNT162b2 mRNA vaccine recipients in New Zealand without previous COVID-19, with enrichment for Māori, Pacific peoples, older adults ≥ 65 years of age, and those with co-morbidities. Serum samples were analysed at baseline and 28 days after second dose for presence of quantitative anti-S IgG by chemiluminescent microparticle immunoassay and for neutralizing capacity against Wuhan, Beta, Delta, and Omicron BA.

The effect of needle length and skin to deltoid muscle distance in adults receiving an mRNA COVID-19 vaccine.

Background: The mRNA COVID vaccines are only licensed for intramuscular injection but it is unclear whether successful intramuscular administration is required for immunogenicity.

Methods: In this observational study, eligible adults receiving their first Comirnaty/BNT162b2 dose had their skin to deltoid muscle distance (SDMD) measured by ultrasound. The relationship between SDMD and height, weight, body mass index, and arm circumference was assessed.

Risk factors for group A streptococcal pharyngitis and skin infections: A case control study.

Background: Group A streptococcal (GAS) infections can trigger an immune-mediated response resulting in acute rheumatic fever (ARF). The role of social and environmental risk factors for GAS pharyngitis and skin infections are not well understood. This study aimed to identify factors associated with GAS pharyngitis and skin infections, and to determine if these are the same as those for ARF.

A controlled human infection model of Streptococcus pyogenes pharyngitis (CHIVAS-M75): an observational, dose-finding study.

Background: Streptococcus pyogenes is a leading cause of infection-related morbidity and mortality. A reinvigorated vaccine development effort calls for new clinically relevant human S pyogenes experimental infection models to support proof of concept evaluation of candidate vaccines. We describe the initial Controlled Human Infection for Vaccination Against S pyogenes (CHIVAS-M75) study, in which we aimed to identify a dose of emm75 S pyogenes that causes acute pharyngitis in at least 60% of volunteers when applied to the pharynx by swab.