Safety and Immunogenicity of 10-valent and 13-valent Pneumococcal Conjugate Vaccines in Papua New Guinean Children

Conditions

Bacteraemia, Meningitis, Otitis Media, Pneumonia, Sepsis

Keywords

pneumococcal, vaccine, papua new guinea

Brief summary

The study aims to evaluate the safety and immunogenicity of the 10-valent and 13-valent pneumococcal conjugate vaccines when administered in an accelerated schedule in Papua New Guinean children, who experience early dense upper respiratory tract colonisation with a broad range of pneumococcal serotypes, and to compare antibody titres following a booster dose of polysaccharide vaccine at 9 months with those children who received no booster at the same age.

Detailed description

The primary aim of the study is to determine whether PCV10 and PCV13 are safe and immunogenic in PNG infants for the serotypes in the respective vaccines. This study is important for the following reasons: 1. There is a lack of data worldwide on immunogenicity in populations with very high early onset of dense URT carriage. 2. The EPI immunisation schedule is very accelerated in PNG (ages 1,2 and 3 months). 3. There are not data on functional antibody to PCVs in PNG. 4. There are no data on NTHi Protein D antibody responses in PNG and worldwide in population with very high URT carriage rates from a young age, i.e. those most likely to benefit from a vaccine including NTHi protein carrier. 5. It is important to investigate impact of vaccine on carriage density in view of our finding of limited impact of 7vPCV on URT carriage. 6. There is no data on antibody responses following 10v or 13v PCV to booster with PPV as young as 9 months of age (which would be the most appropriate within the current PNG EPI schedule and in the many other third world countries). 7. There is no data on antibody responses (including functional assays) to 23vPPV challenge at age 2 years after 23vPPV booster at age 9 months in children primed with PCV. 8. The broad range of serotypes causing IPD in PNG necessitates continuing consideration of 23vPPV as a potential booster at age 9 months. 9. Serotype-specific B cell memory is an important aspect that we can now test to address immunological safety of PPV in children primed with PCV. 10. The Global Alliance for Vaccines and Immunisation (GAVI) and the World Health Organisation (WHO) have committed to the introduction of PCV for infants in GAVI-eligible countries (including PNG) using novel funding mechanism. In PNG, the introduction of a PCV is planned for 2013.

Tilda Orami, Celestine Aho, Rebecca Ford, William Pomat, Andrew R. Greenhill et al. (13 authors)

Vaccine2023-07-206 citations

10.1016/j.vaccine.2023.07.026

Differences in Pneumococcal and Haemophilus influenzae Natural Antibody Development in Papua New Guinean Children in the First Year of Life

Kelly M. Martinovich, Tasmina Rahman, Camilla de Gier, Elke Seppanen, Tilda Orami et al. (19 authors)

Frontiers in Immunology2021-08-107 citations

10.3389/fimmu.2021.725244

PCV10 elicits Protein D IgG responses in Papua New Guinean children but has no impact on NTHi carriage in the first two years of life.

Rahman T, de Gier C, Orami T, Seppanen EJ, Granland CM, Francis JP, Michael A, Yoannes M, Corscadden KJ, Ford RL, Martinovich KM, Jacoby P, van den Biggelaar AHJ, Lehmann D, Richmond PC, Pomat WS, Thornton RB, Kirkham LS.

2021-05-212 citations

10.1016/j.vaccine.2021.05.022

Safety and Immunogenicity of Pneumococcal Conjugate Vaccines in a High-risk Population: A Randomized Controlled Trial of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccine in Papua New Guinean Infants

William Pomat, Anita H.J. van den Biggelaar, Sandra Wana, Jacinta P. Francis, Vela Solomon et al. (55 authors)

Clinical Infectious Diseases2018-08-3138 citations

10.1093/cid/ciy743

Rationale and methods of a randomized controlled trial of immunogenicity, safety and impact on carriage of pneumococcal conjugate and polysaccharide vaccines in infants in Papua New Guinea.

Lehmann D, Kirarock W, van den Biggelaar AHJ, Passey M, Jacoby P, Saleu G, Masiria G, Nivio B, Greenhill A, Orami T, Francis J, Ford R, Kirkham LA, Solomon V, Richmond PC, Pomat WS, 10v13v PCV trial team.

2017-12-257 citations

10.1186/s41479-017-0044-z

Pneumococcal responses are similar in Papua New Guinean children aged 3-5 years vaccinated in infancy with pneumococcal polysaccharide vaccine with or without prior pneumococcal conjugate vaccine, or without pneumococcal vaccination

Anita H.J. van den Biggelaar, Peter Richmond, Angela Fuery, Denise Anderson, Christine Opa et al. (11 authors)

PLoS ONE2017-10-134 citations

10.1371/journal.pone.0185877

Safety and immunogenicity of neonatal pneumococcal conjugate vaccination in Papua New Guinean children: a randomised controlled trial.

Pomat WS, van den Biggelaar AH, Phuanukoonnon S, Francis J, Jacoby P, Siba PM, Alpers MP, Reeder JC, Holt PG, Richmond PC, Lehmann D, Neonatal Pneumococcal Conjugate Vaccine Trial Study Team.

2013-02-2237 citations

10.1371/journal.pone.0056698

Interventions

BIOLOGICALPrevenar 13 and Synflorix

260 children will be randomized to receive either Prevenar 13 or Synflorix at 1-2-3 months. At 9 months 65 children in the Prevenar 13 arm and 65 children in the Synflorix arm will receive booster dose of Pneumovax and at 23 months all children will receive a micro dose of Pneumovax.Blood will be collected at 1, 4, 9, 10, 23 and 24 months to determine serotype-specific antibody responses. Nasopharyngeal swabs will also be collected to measure carriage of pneumococci and non-typeable Haemophilus influenzae.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

28 Days to 35 Days

Healthy volunteers

Yes

Inclusion criteria

* Health infants between 28 - 35 days old

Exclusion criteria

* Infants of women not intending to remain in the are for at least two years * Birth weigh \< 2000 g (2kg) * Severe congenital abnormalities * Mother or child known to be HIV positive

Design outcomes

Primary

Measure	Time frame	Description
Proportion of children with serotype-specific IgG concentration >= 0.35ug/ml at 4 and 9 months of age for 90% of PCV vaccine serotypes and proportion of children with OPA >=1:8 titres at 4, 10 and 24 months	3 years	IgG concentration to vaccine serotypes are \>= 0.35ug/ml post-dose 3 at 4 and 9 months. Serotype-specific IgG concentration \>=0.35ug/ml is protective level against invasive pneumococcal diseases. Opsonophagocytic titre of \>=1:8 examined at 4, 10 and 24 months will inform on functional antibodies induced by vaccination.

Secondary

Measure	Time frame	Description
Compare antibody concentrations to pneumococcal and Haemophilus influenzae protein antigens.	2 years	Measure antibody titres to surface proteins of pneumococci and Hi including Hi protein D, the carrier protein in PCV10 (Synflorix).
Determine carriage rates and bacterial load of pneumococci and H.influenzae	3 years	Proportion of carriage before and after vaccination will be measured using conventional culture methods. Bacterial load will be measured using PCR to determine impact of vaccines
Determine rates of hospital admission for acute respiratory tract infections at 9 and 23 months	2 yrs	Admissions and morbidity for acute respiratory tract infections will be documented at 9 and 23 months.

Countries

Papua New Guinea

Contacts

Primary ContactWilliam Pomat, PhD

william.pomat@pngimr.org.pg+6755322800

Outcome results

None listed