Pneumococcal Vaccines Early and in Combination

Conditions

Otitis Media

Keywords

otitis media, pneumococcal vaccines, randomised controlled trial, high-risk children, indigenous, Australia

Brief summary

The purpose of this study is to determine whether an early schedule of a combination of three doses of PHiD-CV and one dose of PCV13, is superior to three doses of either PCV13 or PHiD-CV.

Detailed description

Aboriginal children in the Northern Territory (NT) have high rates of otitis media caused by non-capsular H. influenzae (NCHi) and pneumococci. Pneumococcal conjugate vaccine has effectively reduced disease caused by the 7 serotypes. Rates of non-vaccine serotype otitis media (OM), particularly 19A is increasing, and NCHi continues to be a major pathogen in perforations. Parallels with pneumonia are highly probable in this population. Vaccines with expanded and early age protection are needed. In early 2009 GSK's pneumococcal H. influenzae protein D conjugate vaccine (PHiD-CV) was licensed in Australia. Compared to the current vaccine, 7PCV, this vaccine offers protection from pneumococcal serotypes 1, 5, 7F as well as NCHi (which is a primary pathogen of OM, and possibly pneumonia). However by 2010, a new generation of Wyeth's 7PCV, PCV13 will also be licensed in Australia. Compared to PHiD-CV this vaccine offers protection from additional serotypes 3, 6A and 19A, however it does not offer protection from NCHi infection. There is no empirical evidence to suggest that either vaccine will have superior clinical efficacy for otitis media or pneumonia in high-risk children. The novel combination strategy proposed for this trial has the potential to provide the best of both vaccines.

Amanda Leach, Nicole Wilson, Beth Arrowsmith, Jemima Beissbarth, Kim Mulholland et al. (22 authors)

PLoS Medicine2024-06-034 citations

10.1371/journal.pmed.1004375

Immunogenicity, otitis media, hearing impairment, and nasopharyngeal carriage 6-months after 13-valent or ten-valent booster pneumococcal conjugate vaccines, stratified by mixed priming schedules: PREVIX_COMBO and PREVIX_BOOST randomised controlled trials.

Leach AJ, Wilson N, Arrowsmith B, Beissbarth J, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Chatfield MD, Lehmann D, Binks M, Chang AB, Carapetis J, Krause V, Andrews R, Snelling T, Skull SA, Licciardi PV, Oguoma VM, Morris PS.

2022-06-2710 citations

10.1016/s1473-3099(22)00272-9

Otitis media outcomes of a combined 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine and 13-valent pneumococcal conjugate vaccine schedule at 1-2-4-6 months: PREVIX_COMBO, a 3-arm randomised controlled trial.

Leach AJ, Mulholland EK, Santosham M, Torzillo PJ, McIntyre P, Smith-Vaughan H, Wilson N, Arrowsmith B, Beissbarth J, Chatfield MD, Oguoma VM, Morris PS.

2021-03-089 citations

10.1186/s12887-021-02552-z

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 conjugate vaccines PREVenar13 and SynflorIX in sequence or alone in high-risk Indigenous infants (PREV-IX_COMBO): protocol of a randomised controlled trial

Amanda Leach, Kim Mulholland, M Santosham, Paul J. Torzillo, Ngiare Joy Brown et al. (14 authors)

BMJ Open2015-01-0127 citations

10.1136/bmjopen-2014-007247

Interventions

DRUGSynflorix

The 10-valent vaccine contains 1 µg of purified capsular polysaccharide of pneumococcal serotypes 1, 5, 6B, 7F, 9V, 14, and 23F conjugated to protein D, 3 µg of serotype 4 conjugated to protein D, 3 µg of serotype 18C conjugated to tetanus toxoid and 3 µg of serotype 19F conjugated to diphtheria toxoid.

DRUGPrevenar13

The vaccine is a ready to use homogeneous white suspension for intramuscular injection, supplied as a pre-filled syringe. Active ingredients Each 0.5 mL dose contains: 2.2 μg of pneumococcal purified capsular polysaccharides for serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F and 23F 4.4 μg of pneumococcal purified capsular polysaccharides for serotype 6B. Each serotype is individually conjugated to non-toxic diphtheria CRM197 protein and adsorbed on aluminium phosphate (0.565 mg). CRM197 is a nontoxic variant of diphtheria toxin isolated from cultures of Corynebacterium diphtheriae strain C7 (β197) grown in a casamino acids and yeast extract-based medium.

DRUGCOMBO

COMBINATION SCHEDULE of vaccine 1 and vaccine 2: Synflorix (PHiD-CV) at 1,2,4 months then Prevenar13 (PCV13) at 6 months of age.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

28 Days to 38 Days

Healthy volunteers

Yes

Inclusion criteria

Indigenous infants * 4 to 6 weeks of age * Living in remote communities that have provided signed Expressions of Interest in participating in PREV-IX\_COMBO trial * Intend to remain in their community until their baby is 7 months of age * Eligible for routine vaccinations.

Exclusion criteria

* Prior adverse reaction to pneumococcal conjugate vaccines according to Australian Immunization Handbook. * Gestational age \< 32 weeks

Design outcomes

Primary

Measure	Time frame	Description
Immunogenicity	7 months of age	At 7 months of age, the overall and serotype specific (particularly serotype 19A and HiD) a IgG Geometric Mean Concentration (GMC) b proportion of children with IgG GMC above threshold (0.35 microg/mL)

Secondary

Measure	Time frame	Description
nasopharyngeal carriage	7 months of age	At 7 months of age, the proportion of children with any carriage of serotype 19A pneumococci
otitis media	7 months of age	At 7 months of age, the proportion of children with any otitis media.

Countries

Australia

Outcome results

None listed