Biology subjects

Licciardi, P. V.

Publications and source records attributed to Licciardi, P. V..

4 recordsLinked to original sources

bioRxiv2024

The Changing Immune Landscape of Innate-like T Cells and Innate Cells Throughout Life

Spectral flow cytometry is an advanced immunological tool that enables comprehensive analysis of the immune system by simultaneously comparing innate and adaptive immune cells. Here, using a 40-colour antibody panel we advance our knowledge of innate and innate-like T cells by investigating chemokine receptors, activation and maturation markers not usually assessed on these populations and examine age-related effects to these immune cell subsets. We characterised phenotypic changes of peripheral blood mononuclear cells (PBMC) in three age groups: newborn (cord blood), adults aged 20-30 years, and adults aged 70-80 years, focusing on innate-like T cells and innate cells, including MAIT cells, NKT cells, {gamma}{delta} T cells, ILCs, and Natural Killer (NK) cells. We identify subsets of double-negative (DN) T cells (CD4- CD8-) and CD161+ T cells that increase in an age-related manner and exhibit a phenotype similar to innate-like T cells, MAIT cells and {gamma}{delta} T cells. Innate-like T cell subsets express similar patterns of the chemokine receptors and maturation markers CCR4, CCR6, CD27, CD38, CD57 and CD45RA, and resemble memory subsets of conventional CD4+ T cells and CD8+ T cells. We could detect ILCs in all age ranges, although the frequency of ILC1, ILC2, and ILC3 subsets decreased with age. Notably, we identify the NK maturation marker, CD57, as a universal marker that defines ageing populations of innate and adaptive immune cells. This study enhances our understanding of the ontogeny of human immune cells, highlighting significant age-related changes in the frequency and phenotype of immune cells.

immunology↗

bioRxiv2024

Streptococcus pyogenes pharyngitis elicits diverse antibody responses to key vaccine antigens influenced by the imprint of past infections.

Knowledge gaps regarding human immunity to Streptococcus pyogenes have impeded vaccine development. To address these gaps and evaluate vaccine candidates, we established a human challenge model of S. pyogenes pharyngitis. Here, we analysed antibody responses in serum and saliva against 19 antigens to identify characteristics distinguishing 19 participants who developed pharyngitis and 6 who did not. Pharyngitis elicited serum IgG responses to key vaccine antigens and a muted mucosal IgA response, whereas the 6 participants without pharyngitis had more pronounced IgA responses and minimal IgG responses. Serum IgG responses to pharyngitis in adult participants resembled those observed in children and were inversely correlated with the magnitude of pre-existing responses. While a straightforward correlate of protection was not evident, baseline antibody signatures distinguished clinical and immunological outcomes following experimental challenge. This highlights the influence of a complex humoral imprint from previous exposure, relevant for interpreting immunogenicity in forthcoming vaccine trials.

immunology↗

bioRxiv2023

Streptococcus pneumoniae serotype 33G: genetic, serological, and structural analysis of a new capsule type

Streptococcus pneumoniae (the pneumococcus) is a human pathogen responsible for a spectrum of diseases such as pneumonia, sepsis, and meningitis. The capsule is the major pneumococcal virulence factor and is encoded by the capsular polysaccharide (cps) locus, a recombination hot spot that has resulted in over 100 distinct capsular polysaccharide types (serotypes) identified to date. Recently, 33X (also known as 10X) was proposed as a putative novel serotype, but the capsule structure had not been elucidated. Here, we provide an in-depth investigation of 33X, demonstrating it is a new pneumococcal capsular serotype. In this study, we screened 12,850 nasopharyngeal swabs from both healthy children and pneumonia patients (adults and children) in Mongolia collected between 2015-2022. We identified 20 pneumococcal 33X isolates. Using whole genome sequencing, we found that the 33X cps locus is a chimera of genes from pneumococcal serogroups 35, 10 and 33, as well as other Streptococcal species. Serotyping of 33X pneumococci by the Quellung reaction revealed a unique serological profile, typing as both 10B and 33B. Competitive ELISAs confirmed that antibodies that were generated in mice directed against 33X were inhibited by 33X pneumococci but not 10B or 33B. Lastly, elucidation of the 33X capsule structure revealed that the polysaccharide is distinct from other serotypes, consisting of an O-acetylated hexasaccharide repeat unit of [->]5)-{beta}-Galf-(1[->]3)-{beta}-Glcp-(1[->]5)-{beta}-Galf 2Ac-(1[->]3)-{beta}-GalpNAc-(1[->]3)--Galp-(1[->]4)-Rib-ol-(5[->]P[->]. Therefore, 33X meets the requisite genetic, serological, and biochemical criteria to be designated as a new serotype, which we have named 33G. IMPORTANCEStreptococcus pneumoniae (the pneumococcus) is a bacterial pathogen with the greatest burden of disease in Asia and Africa. The pneumococcal capsular polysaccharide has biological relevance as a major virulence factor, as well as public health importance as it is the target for currently licensed vaccines. These vaccines have limited valency, covering up to 23 of the >100 known capsular types (serotypes) with higher valency vaccines in development. Here, we have characterized a new pneumococcal serotype, which we have named 33G. We detected serotype 33G in nasopharyngeal swabs (n=20) from children and adults hospitalized with pneumonia, as well as healthy children in Mongolia. We show that the genetic, serological, and biochemical properties of 33G differs from existing serotypes, satisfying the criteria to be designated as a new serotype. Future studies should focus on the geographical distribution of 33G and any changes in prevalence following vaccine introduction.

microbiology↗

bioRxiv2023

Therapeutic immunization with a whole cell vaccine reduces pneumococcal nasopharyngeal density, shedding, and middle ear infection in mice

Pneumococcal Conjugate Vaccines (PCVs) have substantially reduced the burden of disease caused by Streptococcus pneumoniae (the pneumococcus). However, protection is limited to vaccine serotypes, and when administered to children who are colonized with pneumococci at the time of vaccination, immune responses to the vaccine are blunted. Here, we investigate the potential of a killed whole cell pneumococcal vaccine (WCV) to reduce existing pneumococcal carriage and mucosal disease when given therapeutically to infant mice colonized with pneumococci. We show that a single dose of WCV reduced pneumococcal carriage density in an antibody-dependent manner. Therapeutic vaccination induced robust immune responses to pneumococcal surface antigens CbpA, PspA (family 1) and PiaA. In a co-infection model of otitis media, a single dose of WCV reduced pneumococcal middle ear infection. Lastly, in a two-dose model, therapeutic administration of WCV reduced nasal shedding of pneumococci. Taken together, our data demonstrate that WCV administered in colonized mice reduced pneumococcal density in the nasopharynx and the middle ear, and decreased shedding. A vaccine with similar properties in children would be beneficial in low and middle-income settings where pneumococcal carriage is high. ImportanceAlthough typically asymptomatic, pneumococcal carriage plays an essential role in transmission and the development of disease. Pneumococcal Conjugate Vaccines (PCVs) have reduced the burden of pneumococcal disease worldwide. However, their use has increased carriage and disease caused by non-vaccine serotypes, prompting investigations into serotype-independent pneumococcal vaccines. An additional limitation of PCVs is immune hypo-responsiveness to vaccines in children carrying pneumococci at the time of vaccination. Therefore, there is great interest in next generation vaccines such as whole cell vaccines. In this study we investigate a pneumococcal whole cell vaccine (WCV) for it effect on carriage in mice that are already colonized at the time of vaccination. We show that this therapeutic vaccination of mice can reduce pneumococcal carriage density, shedding and infection of the middle ear. Our study suggests that WCV could be beneficial in high burden settings where carriage at the time of vaccination is more common.

microbiology↗