A longitudinal study of natural antibody development to pneumococcal surface protein A families 1 and 2 in Papua New Guinean Highland children: a cohort study

Jacinta P Francis, Peter C Richmond, Audrey Michael, Peter M Siba, Peter Jacoby, Belinda J Hales, Wayne R Thomas, Deborah Lehmann, William S Pomat, Anita H J van den Biggelaar, Jacinta P Francis, Peter C Richmond, Audrey Michael, Peter M Siba, Peter Jacoby, Belinda J Hales, Wayne R Thomas, Deborah Lehmann, William S Pomat, Anita H J van den Biggelaar

Abstract

Background: Pneumococcal surface protein A (PspA), a conserved virulence factor essential for Streptococcus pneumoniae attachment to upper respiratory tract (URT) epithelia, is a potential vaccine candidate for preventing colonisation.

Methods: This cohort study was conducted in the Asaro Valley in the Eastern Highlands Province of Papua New Guinea, of which Goroka town is the provincial capital. The children included in the analysis were participants in a neonatal pneumococcal conjugate vaccine trial (ClinicalTrials.gov NCT00219401) that was conducted between 2005 and 2009. We investigated the development of anti-PspA antibodies in the first 18 months of life relative to URT pneumococcal carriage in Papua New Guinean infants who experience one of the earliest and highest colonisation rates in the world. Blood samples and nasopharyngeal swabs were collected from a cohort of 88 children at ages 3, 9, and 18 months to quantify immunoglobulin G (IgG) levels to PspA families 1 and 2 using an enzyme-linked immunosorbent assay and to determine URT carriage.

Results: Seventy-three per cent (64/88) of infants carried S. pneumoniae at age 3 months; 85 % (75/88) at 9 months, and 83 % (73/88) at 18 months. PspA-IgG levels declined between ages 3 and 9 months (p < 0.001), then increased between 9 and 18 months (p < 0.001). At age 3 months, pneumococcal carriers showed lower PspA1-IgG levels (geometric mean concentration [GMC] 602 arbitrary units [AU]/ml, 95 % confidence interval [CI] 497-728) than non-carriers (GMC 1058 AU/ml [95 % CI 732-1530]; p = 0.008), while at 9 months, PspA1- and PspA2-IgG levels were significantly higher in carriers (PspA1: 186 AU/ml, 95 % CI 136-256; PspA2: 284 AU/ml, 95 % CI 192-421) than in non-carriers (PspA1 87 AU/ml, 95 % CI 45-169; PspA2 74 AU/ml, 95 % CI 34-159) (PspA1: p = 0.037, PspA2: p = 0.003).

Conclusion: Our findings confirm that PspA is immunogenic and indicate that natural anti-PspA immune responses are acquired through exposure and develop with age. PspA may be a useful candidate in an infant pneumococcal vaccine to prevent early URT colonisation.

Keywords: Children; Natural immunity; Papua New Guinea; PspA; Streptococcus pneumoniae; Vaccine.

Figures

Fig. 1
Fig. 1
Geometric mean concentrations (GMC) of IgG responses to PspA1 (a) and PspA2 (b) in relation to age. Error bars indicate 95 % confidence intervals of the GMC. PspA, pneumococcal surface protein A; AU/ml, arbitrary ELISA units/ml
Fig. 2
Fig. 2
Geometric mean concentrations (GMC) of IgG responses to PspA1 (a) and PspA2 (b) in non-carrier (grey bars) and Streptococcus pneumoniae carrier (black bars) infants at 3, 9, and 18 months of age. Error bars indicate 95 % confidence intervals of the GMC. ✩ p ≤ 0.05 is considered a statistically significant difference. PspA, pneumococcal surface protein A; AU/ml, arbitrary ELISA units/ml

References

    1. Izadnegahdar R, Cohen AL, Klugman KP, Qazi SA. Childhood pneumonia in developing countries. Lancet Respir Med. 2013;1:574–84. doi: 10.1016/S2213-2600(13)70075-4.
    1. Zar HJ, Ferkol TW. The global burden of respiratory disease-impact on child health. Pediatr Pulmonol. 2014;49:430–4. doi: 10.1002/ppul.23030.
    1. Sa’avu M, Duke T, Matai S. Improving paediatric and neonatal care in rural district hospitals in the highlands of Papua New Guinea: a quality improvement approach. Paediatr Int Child Health. 2014;34:75–83. doi: 10.1179/2046905513Y.0000000081.
    1. Francis JP, Richmond PC, Pomat WS, Michael A, Keno H, Phuanukoonnon S, et al. Maternal antibodies to pneumolysin but not to pneumococcal surface protein A delay early pneumococcal carriage in high-risk Papua New Guinean infants. Clin Vaccine Immunol. 2009;16:1633–8. doi: 10.1128/CVI.00247-09.
    1. Leach AJ, Boswell JB, Asche V, Nienhuys TG, Mathews JD. Bacterial colonization of the nasopharynx predicts very early onset and persistence of otitis media in Australian aboriginal infants. Pediatr Infect Dis J. 1994;13:983–9. doi: 10.1097/00006454-199411000-00009.
    1. Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA, Cherian T, Serotype Replacement Study Group et al. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med. 2013;10:e1001517. doi: 10.1371/journal.pmed.1001517.
    1. Hammitt LL, Akech DO, Morpeth SC, Karani A, Kihuha N, Nyongesa S, et al. Population effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and non-typeable Haemophilus influenzae in Kilifi, Kenya: findings from cross-sectional carriage studies. Lancet Glob Health. 2014;2:e397–405. doi: 10.1016/S2214-109X(14)70224-4.
    1. Hammitt LL, Ojal J, Bashraheil M, Morpeth SC, Karani A, Habib A, et al. Immunogenicity, impact on carriage and reactogenicity of 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Kenyan children aged 1-4 years: a randomized controlled trial. PLoS One. 2014;9:e85459. doi: 10.1371/journal.pone.0085459.
    1. Henriques-Normark B, Blomberg C, Dagerhamn J, Bättig P, Normark S. The rise and fall of bacterial clones: Streptococcus pneumoniae. Nat Rev Microbiol. 2008;6:827–37. doi: 10.1038/nrmicro2011.
    1. Pittet LF, Posfay-Barbe KM. Pneumococcal vaccines for children: a global public health priority. Clin Microbiol Infect. 2012;18(Suppl 5):25–36. doi: 10.1111/j.1469-0691.2012.03938.x.
    1. Prescott SL, Taylor A, King B, Dunstan J, Upham JW, Thornton CA, et al. Neonatal interleukin-12 capacity is associated with variations in allergen-specific immune responses in the neonatal and postnatal periods. Clin Exp Allergy. 2003;33:566–72. doi: 10.1046/j.1365-2222.2003.01659.x.
    1. Ren B, McCrory MA, Pass C, Bullard DC, Ballantyne CM, Xu Y, et al. The virulence function of Streptococcus pneumoniae surface protein A involves inhibition of complement activation and impairment of complement receptor-mediated protection. J Immunol. 2004;173:7506–12. doi: 10.4049/jimmunol.173.12.7506.
    1. Ren B, Szalai AJ, Thomas O, Hollingshead SK, Briles DE. Both family 1 and family 2 PspA proteins can inhibit complement deposition and confer virulence to a capsular serotype 3 strain of Streptococcus pneumoniae. Infect Immun. 2003;71:75–85. doi: 10.1128/IAI.71.1.75-85.2003.
    1. Briles DE, Hollingshead SK, Paton JC, Ades EW, Novak L, van Ginkel FW, et al. Immunizations with pneumococcal surface protein A and pneumolysin are protective against pneumonia in a murine model of pulmonary infection with Streptococcus pneumoniae. J Infect Dis. 2003;188:339–48. doi: 10.1086/376571.
    1. Miyaji EN, Dias WO, Gamberini M, Gebara VC, Schenkman RP, Wild J, et al. PsaA (pneumococcal surface adhesin A) and PspA (pneumococcal surface protein A) DNA vaccines induce humoral and cellular immune responses against Streptococcus pneumoniae. Vaccine. 2001;20:805–12. doi: 10.1016/S0264-410X(01)00395-4.
    1. Ogunniyi AD, Grabowicz M, Briles DE, Cook J, Paton JC. Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae. Infect Immun. 2007;75:350–7. doi: 10.1128/IAI.01103-06.
    1. Palaniappan R, Singh S, Singh UP, Sakthivel SK, Ades EW, Briles DE, et al. Differential PsaA-, PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriage. Infect Immun. 2005;73:1006–13. doi: 10.1128/IAI.73.2.1006-1013.2005.
    1. Hales BJ, Chai LY, Elliot CE, Pearce LJ, Zhang G, Heinrich TK, et al. Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children. Thorax. 2012;67:321–7. doi: 10.1136/thoraxjnl-2011-200650.
    1. Holmlund E, Quiambao B, Ollgren J, Nohynek H, Käyhty H. Development of natural antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A and pneumolysin in Filipino pregnant women and their infants in relation to pneumococcal carriage. Vaccine. 2006;24:57–65. doi: 10.1016/j.vaccine.2005.07.055.
    1. Melin MM, Hollingshead SK, Briles DE, Lahdenkari MI, Kilpi TM, Käyhty HM. Development of antibodies to PspA families 1 and 2 in children after exposure to Streptococcus pneumoniae. Clin Vaccine Immunol. 2008;15:1529–35. doi: 10.1128/CVI.00181-08.
    1. Simell B, Melin M, Lahdenkari M, Briles DE, Hollingshead SK, Kilpi TM, et al. Antibodies to pneumococcal surface protein A families 1 and 2 in serum and saliva of children and the risk of pneumococcal acute otitis media. J Infect Dis. 2007;196:1528–36. doi: 10.1086/522607.
    1. Laine C, Mwangi T, Thompson CM, Obiero J, Lipsitch M, Scott JA. Age-specific immunoglobulin g (IgG) and IgA to pneumococcal protein antigens in a population in coastal Kenya. Infect Immun. 2004;72:3331–5. doi: 10.1128/IAI.72.6.3331-3335.2004.
    1. Turner P, Turner C, Green N, Ashton L, Lwe E, Jankhot A, et al. Serum antibody responses to pneumococcal colonization in the first 2 years of life: results from an SE Asian longitudinal cohort study. Clin Microbiol Infect. 2013;19:E551–8. doi: 10.1111/1469-0691.12286.
    1. Darrieux M, Miyaji EN, Ferreira DM, Lopes LM, Lopes AP, Ren B, et al. Fusion proteins containing family 1 and family 2 PspA fragments elicit protection against Streptococcus pneumoniae that correlates with antibody-mediated enhancement of complement deposition. Infect Immun. 2007;75:5930–8. doi: 10.1128/IAI.00940-07.
    1. Phuanukoonnon S, Reeder JC, Pomat WS, Van den Biggelaar AH, Holt PG, Saleu G, Neonatal Pneumococcal Conjugate Vaccine Trial Study Team et al. A neonatal pneumococcal conjugate vaccine trial in Papua New Guinea: study population, methods and operational challenges. P N G Med J. 2010;53:191–206.
    1. O’Brien KL, Nohynek H, World Health Organization Pneumococcal Vaccine Trials Carriage Working Group Report from a WHO working group: standard method for detecting upper respiratory carriage of Streptococcus pneumoniae. Pediatr Infect Dis J. 2003;22:133–40.
    1. Gratten M, Montgomery J. The bacteriology of acute pneumonia and meningitis in children in Papua New Guinea: assumptions, facts and technical strategies. P N G Med J. 1991;34:185–98.
    1. Montgomery JM, Lehmann D, Smith T, Michael A, Joseph B, Lupiwa T, et al. Bacterial colonization of the upper respiratory tract and its association with acute lower respiratory tract infections in Highland children of Papua New Guinea. Rev Infect Dis. 1990;12(Suppl 8):S1006–16. doi: 10.1093/clinids/12.Supplement_8.S1006.
    1. Pomat WS, van den Biggelaar AH, Phuanukoonnon S, Francis J, Jacoby P, Siba PM, Neonatal Pneumococcal Conjugate Vaccine Trial Study Team et al. Safety and immunogenicity of neonatal pneumococcal conjugate vaccination in Papua New Guinean children: a randomised controlled trial. PLoS One. 2013;8:e56698. doi: 10.1371/journal.pone.0056698.
    1. Aho C, Greenhill A, Phuanukoonnon S, Michael A, Moberly S, Pomat W, et al. Impact of neonatal and early infant pneumococcal conjugate vaccination on pneumococcal carriage and suppurative otitis media in Papua New Guinea. Tel Aviv: Seventh International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD 7); 2010.
    1. Keck JW, Wenger JD, Bruden DL, Rudolph KM, Hurlburt DA, Hennessy TW, et al. PCV7-induced changes in pneumococcal carriage and invasive disease burden in Alaskan children. Vaccine. 2014;32:6478–84. doi: 10.1016/j.vaccine.2014.09.037.

Source: PubMed

Sponzoři a spolupracovníci

Zdravotní podmínky

Drogové intervence

3
Předplatit