William Pomat | Papua New Guinea Institute Of Medical Research (original) (raw)

Papers by William Pomat

Vaccine, 2009

The effects of neonatal immunization with 7-valent pneumococcal conjugate vaccine (7vPCV) on deve... more The effects of neonatal immunization with 7-valent pneumococcal conjugate vaccine (7vPCV) on development of T-cell memory and general immune maturation were studied in a cohort of Papua New Guinean newborns. Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM 197 compared to 7vPCV at 1 and 2 months of age only. T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls. Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.

Clinical and Vaccine Immunology, 2009

Immunization of pregnant women can be an efficient strategy to induce early protection in infants... more Immunization of pregnant women can be an efficient strategy to induce early protection in infants in developing countries. Pneumococcal protein-based vaccines may have the capacity to induce pneumococcal serotype-independent protection. To understand the potential of maternal pneumococcal protein-specific antibodies in infants in high-risk areas, we studied the placental transfer of naturally acquired antibodies to pneumolysin (Ply) and pneumococcal surface protein A family 1 and 2 (PspA1 and PspA2) in relation to onset of pneumococcal nasopharyngeal carriage in infants in Papua New Guinea (PNG). In this study, 76% of the infants carried Streptococcus pneumoniae in the upper respiratory tract within the first month of life, at a median age of 19 days. Maternal and cord blood antibody titers to Ply ( ‫؍‬ 0.824, P < 0.001), PspA1 ( ‫؍‬ 0.746, P < 0.001), and PspA2 ( ‫؍‬ 0.631, P < 0.001) were strongly correlated. Maternal pneumococcal carriage (hazard ratio [HR], 2.60; 95% confidence interval [CI], 1.25 to 5.39) and younger maternal age (HR, 0.74; 95% CI, 0.54 to 1.00) were independent risk factors for early carriage, while higher cord Ply-specific antibody titers predicted a significantly delayed onset (HR, 0.71; 95% CI, 0.52 to 1.00) and cord PspA1-specific antibodies a significantly younger onset of carriage in PNG infants (HR, 1.57; 95% CI, 1.03 to 2.40). Maternal vaccination with a pneumococcal protein-based vaccine should be considered as a strategy to protect high-risk infants against pneumococcal disease by reducing carriage risks in both mothers and infants.

Clinical and Experimental Immunology, 2008

Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua New Guinean child... more Antibodies against pneumococcal polysaccharides were measured by ELISA in Papua New Guinean children with pneumonia aged 0–14 months, in age-matched healthy Papua New Guinean controls and in healthy expatriate children living in Papua New Guinea. At 0–5 months of age, the IgG antibody titres against six of the eight polysaccharides measured were significantly lower in pneumonia patients than in both control groups. Antibody titres in 6–14-month-old Papua New Guinean controls were significantly lower than in control Papua New Guineans aged 0–5 months for five of the eight polysaccharides tested. In the 6–14-months age group the antibody titre was significantly lower in pneumonia patients than in controls for only one polysaccharide. For seven of the eight serotypes tested, antibody levels in expatriate controls did not decline with age. Antibody responses of Papua New Guinean children aged 6–18 months to a 23-valent pneumococcal vaccine were serotype dependent. Fold increases in response to the vaccine were greatest for the IgA isotype. IgG antibody responses were greater than three fold to four of the eight serotypes tested.

Immunogenetics

We have analysed the transcribed immunoglobulin kappa (IGK) repertoire of peripheral blood B cell... more We have analysed the transcribed immunoglobulin kappa (IGK) repertoire of peripheral blood B cells from four individuals from two genetically distinct populations, Papua New Guinean and Australian, using high-throughput DNA sequencing. The depth of sequencing data for each individual averaged 5,548 high-quality IGK reads, and permitted genotyping of the inferred IGKV and IGKJ germline gene segments for each individual. All individuals were homozygous at each IGKJ locus and had highly similar inferred IGKV genotypes. Preferential gene usage was seen at both the IGKV and IGKJ loci, but only IGKV segment usage varied significantly between individuals. Despite the differences in IGKV gene utilisation, the rearranged IGK repertoires showed extensive identity at the amino acid level. Public rearrangements (those shared by two or more individuals) made up 60.2% of the total sequenced IGK rearrangements. The total diversity of IGK rearrangements of each individual was estimated to range from just 340 to 549 unique amino acid sequences. Thus, the repertoire of unique expressed IGK rearrangements is dramatically less than previous theoretical estimates of IGK diversity, and the majority of expressed IGK rearrangements are likely to be extensively shared in individual human beings.

Vaccine, 2011

Concerns about the risk of inducing immune deviation-associated “neonatal tolerance” as described... more Concerns about the risk of inducing immune deviation-associated “neonatal tolerance” as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n = 104) or at 1, 2 and 3 months of age (infant group, n = 105), or to not receive 7vPCV at all (control group, n = 109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-γ) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM197 and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.

Immunogenetics, 2011

Complete and accurate knowledge of the genes and allelic variants of the human immunoglobulin gen... more Complete and accurate knowledge of the genes and allelic variants of the human immunoglobulin gene loci is critical for studies of B cell repertoire development and somatic point mutation, but evidence from studies of VDJ rearrangements suggests that our knowledge of the available immunoglobulin gene repertoire is far from complete. The reported repertoire has changed little over the last 15 years. This is, in part, a consequence of the inefficiencies involved in searching for new members of large, multigenic gene families by cloning and sequencing. The advent of high-throughput sequencing provides a new avenue by which the germline repertoire can be explored. In this report, we describe pyrosequencing studies of the heavy chain IGHV1, IGHV3 and IGHV4 gene subgroups in ten Papua New Guineans. Thousands of 454 reads aligned with complete identity to 51 previously reported functional IGHV genes and allelic variants. A new gene, IGHV3-NL1*01, was identified, which differs from the nearest previously reported gene by 15 nucleotides. Sixteen new IGHV alleles were also identified, 15 of which varied from previously reported functional IGHV genes by between one and four nucleotides, while one sequence appears to be a functional variant of the pseudogene IGHV3-25. BLAST searches suggest that at least six of these new genes are carried within the relatively well-studied populations of North America, Europe or Asia. This study substantially expands the known immunoglobulin gene repertoire and demonstrates that genetic variation of immunoglobulin genes can now be efficiently explored in different human populations using high-throughput pyrosequencing.

Journal of Allergy and Clinical Immunology, 2009

The protective effect of Mycobacterium bovis BCG vaccination against infection and atopy varies b... more The protective effect of Mycobacterium bovis BCG vaccination against infection and atopy varies between populations.To identify differences in neonatal responses to BCG between diverse populations and study longitudinal associations with memory T-cell responses.Cord blood mononuclear cells were collected from Papua New Guinean (PNG) and Western Australian (WA) newborns. Toll-like receptor (TLR)-2, TLR4, and TLR9 mRNA expression and in vitro BCG-stimulated (±IFN-γ priming) innate cytokine responses were compared. When PNG infants were 3 months old, PBMCs were stimulated in vitro with Mycobacterium-purified protein derivative (PPD) to determine memory T-cell responses.BCG-induced IL-10 and IFN-γ responses were significantly higher in cord blood mononuclear cells of PNG newborns, and TLR2 and TLR9 expression was significantly higher and TLR4 expression lower compared with WA newborns. High neonatal IL-10 and low IFN-γ responses to BCG were found to promote the development of PPD-memory TH2 responses in infancy, whereas neonatal BCG-TNFα responses inhibited the development of PPD-IL 10 responses. When primed with IFN-γ, BCG-induced TNF-α, IL-12p70, and in particular IFN-γ responses were enhanced to a significantly higher extent in WA than in PNG newborns. In response to IFN-γ priming and BCG stimulation, natural killer cells of WA newborns produced IFN-γ, whereas natural killer cells of PNG newborns contributed only indirectly to this response.Neonatal BCG-related innate immune responses control the differentiation of TH memory responses and vary between populations. This may explain differences in the effects of BCG vaccination between populations.

Vaccine, 2003

In two studies, pneumococcal polysaccharide (Pnc PS) vaccine was given to more than 400 pregnant ... more In two studies, pneumococcal polysaccharide (Pnc PS) vaccine was given to more than 400 pregnant Papua New Guinean women. No deleterious effects were found. The vaccine prevented acute lower respiratory infection (ALRI) among offspring in utero or aged 1–17 months at the time of maternal immunisation, suggesting protection through breast feeding. Serum IgG antibody titres were higher in vaccinated than unvaccinated groups for 2–4 months after delivery and no immune suppression, evaluated by the response to subsequent Pnc PS vaccination, was detected. Breast milk IgA to four serotypes was 1.1–1.8 times higher in immunised than unimmunised women for 6 months postpartum. Given results from several developing countries, large-scale safety and efficacy trials are now justified. Postpartum maternal immunisation is another intervention under consideration.

Vaccine, 2002

In Tari, Southern Highlands Province (SHP), Papua New Guinea (PNG), pneumococcal polysaccharide (... more In Tari, Southern Highlands Province (SHP), Papua New Guinea (PNG), pneumococcal polysaccharide (Pnc PS) vaccine was offered to women at 28–38 weeks gestation. Blood samples were collected for measurement of pneumococcal antibody titres prior to immunization, from mother and cord at delivery and from their children at ages 1–3 and 4–6 months; samples were also collected in a subset of children before and 1 month after Pnc PS vaccine was given at age 8–9 months. Serum was collected from unimmunized women and their children at delivery and from children of unimmunized women at the same ages in infancy. There were no differences in neonatal or post-neonatal mortality rates or congenital abnormalities in the children of 235 immunized and 202 unimmunized women. There was a significant increase in antibody titres to pneumococcal serotypes 5, 14 and 23F in immunized women but not for serotype 7F. Geometric mean titres (GMTs) of antibodies for serotypes 5 and 23F were significantly higher in children of immunized women than in the unimmunized group up to age 2 months and for serotype 14 significantly higher to age 4 months. Maternal immunization did not significantly affect the children’s capacity to make antibody responses to immunization with Pnc PS vaccine in infancy. The findings of this study and those in several other developing countries provide support for the concept of Pnc PS maternal immunization and justify the planning of large-scale efficacy trials.

Pediatric Infectious Disease Journal, 1989

Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > August ...