Evaluation of the safety and immunogenicity in United Kingdom laboratory workers of a combined Haemophilus influenzae type b and meningococcal capsular group C conjugate vaccine

Jamie Findlow, Helen Findlow, Sarah Frankland, Ann Holland, Daniel Holme, Emma Newton, Jo Southern, Pauline Waight, Ed Kaczmarski, Elizabeth Miller, Ray Borrow, Jamie Findlow, Helen Findlow, Sarah Frankland, Ann Holland, Daniel Holme, Emma Newton, Jo Southern, Pauline Waight, Ed Kaczmarski, Elizabeth Miller, Ray Borrow

Abstract

Background: Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort.

Methods: A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses.

Results: At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced > 3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres ≥ 8, 100% had short term protective anti-Hib PRP IgG concentrations ≥ 0.15 μg/mL and 97% had protective anti-tetanus toxoid concentrations ≥ 0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects.

Conclusions: Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting.

Keywords: Haemophilus influenzae type b; Laboratory workers; Meningococcal; Occupational immunisation; Tetanus; Vaccine.

Figures

Figure 1
Figure 1
Participant flow chart.

References

    1. Ladhani SN. Two decades of experience with the Haemophilus influenzae serotype b conjugate vaccine in the United Kingdom. Clin Ther. 2012;34:385–399. doi: 10.1016/j.clinthera.2011.11.027.
    1. Miller E, Salisbury D, Ramsay M. Planning, registration, and implementation of an immunisation campaign against meningococcal serogroup C disease in the UK: a success story. Vaccine. 2001;20(Supplement 1):S58–S67.
    1. Balmer P, Borrow R, Miller E. Impact of meningococcal C conjugate vaccine in the UK. J Med Microbiol. 2002;51:717–722.
    1. Boutet R, Stuart JM, Kaczmarski EB, Gray SJ, Jones DM, Andrews N. Risk of laboratory-acquired meningococcal disease. J Hosp Infect. 2001;49:282–284. doi: 10.1053/jhin.2001.1084.
    1. Health and Safety Executive, Health Services Advisory Committee. Safe Working and the Prevention of Infection in Clinical Laboratories and Similar Facilities. London, UK: HSE Books; 2003.
    1. Kessler AT, Stephens DS, Somani J. Laboratory-acquired serogroup A meningococcal meningitis. J Occup Health. 2007;49:399–401. doi: 10.1539/joh.49.399.
    1. Athlin S, Vikerfors T, Fredlund HH, Olcén P. Atypical clinical presentation of laboratory-acquired meningococcal disease. Scand J Infect Dis. 2007;2007(39):911–913.
    1. Bhatti AR, DiNinno VL, Ashton FE, White LA. A laboratory-acquired infection with Neisseria meningitidis. J Infect. 1982;4:247–252. doi: 10.1016/S0163-4453(82)92563-4.
    1. Omer H, Rose G, Jolley KA, Frapy E, Zahar JR, Maiden MC, Bentley SD, Tinsley CR, Nassif X, Bille E. Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage. PLoS One. 2011;6:e17145. doi: 10.1371/journal.pone.0017145. 10.1371/journal.pone.0017145.
    1. From the Centers for Disease Control and Prevention. Laboratory-acquired meningococcal disease--United States, 2000. JAMA. 2002;287:1256–1258.
    1. Department of Health. Immunisation against infectious disease - ‘the green book’.
    1. Balmer P, Falconer M, McDonald P, Andrews N, Fuller E, Riley C, Kaczmarski E, Borrow R. Immune response to meningococcal serogroup C conjugate vaccination in asplenic individuals. Infect Immun. 2004;72:332–337. doi: 10.1128/IAI.72.1.332-337.2004.
    1. Lal G, Balmer P, Joseph H, Dawson M, Borrow R. Development and evaluation of a tetraplex flow cytometric assay for quantitation of serum antibodies to Neisseria meningitidis serogroups A, C, Y, and W-135. Clin Diagn Lab Immunol. 2004;11:272–279.
    1. Pickering JW, Martins TB, Schroder MC, Hill HR. Comparison of a multiplex flow cytometric assay with enzyme-linked immunosorbent assay for quantitation of antibodies to tetanus, diphtheria, and Haemophilus influenzae type b. Clin Diagn Lab Immunol. 2002;9:872–876.
    1. Maslanka SE, Gheesling LL, LiButti DE, Donaldson KBJ, Harakeh HS, Dykes JK, Arhin FF, Devi SJN, Frasch CE, Huang JC, Kris-Kuzemenska P, Lemmon RD, Lorange M, Peeters CCAM, Quataert S, Tai JY, Carlone GM. Standardization and a multilaboratory comparison of Neisseria meningitidis serogroup A and C serum bactericidal assays. Clin Diag Lab Immunol. 1997;4:156–167.
    1. Andrews N, Borrow R, Miller E. Validation of serological correlate of protection for meningococcal C conjugate vaccine using efficacy estimates from post-licensure surveillance in England. Clin Diag Lab Immunol. 2003;10:780–786.
    1. Kayhty H, Peltola H, Karanko V, Makela PH. The protective level of serum antibodies to the capsular polysaccharide of Haemophilus influenzae type b. J Infect Dis. 1983;147:1100. doi: 10.1093/infdis/147.6.1100.
    1. Borrow R, Balmer P, Roper MH. The Immunological Basis for Immunisation Series. Module 3: Tetanus. Geneva, Switzerland: World Health Organization; 2007.
    1. Borrow R, Andrews N, Goldblatt D, Miller E. Serological basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: a re-evaluation of correlates of protection. Infect Immun. 2001;69:1568–1573. doi: 10.1128/IAI.69.3.1568-1573.2001.
    1. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus: I. The role of humoral antibodies. J Exp Med. 1969;129:1307–1326. doi: 10.1084/jem.129.6.1307.
    1. Goldschneider I, Gotschlich EC, Artenstein MS. Human immunity to the meningococcus: II. Development of natural immunity. J Exp Med. 1969;129:1327–1348. doi: 10.1084/jem.129.6.1327.
    1. Maple PA, Jones CS, Wall EC, Vyse A, Edmunds WJ, Andrews NJ, Miller E. Immunity to diphtheria and tetanus in England and Wales. Vaccine. 2000;19:167–173. doi: 10.1016/S0264-410X(00)00184-5.
    1. Ishola DA, Borrow R, Findlow H, Findlow J, Trotter C, Ramsay ME. Prevalence of serum bactericidal antibody to serogroup C Neisseria meningitidis in England a decade after vaccine introduction. Clin Vaccine Immunol. 2012;19:1126–1130. doi: 10.1128/CVI.05655-11.
    1. Borrow R, Southern J, Andrews N, Peake N, Rahim R, Acuna M, Martin S, Miller E, Kaczmarski E. Comparison of antibody kinetics following meningococcal serogroup C conjugate vaccine between healthy adults previously vaccinated with meningococcal A/C polysaccharide vaccine and vaccine-naïve controls. Vaccine. 2001;19:2050–3043.
    1. Findlow J, Taylor S, Aase A, Horton R, Heyderman R, Southern J, Andrews N, Barchha R, Harrison E, Lowe A, Boxer E, Heaton C, Balmer P, Kaczmarski E, Oster P, Gorringe A, Borrow R, Miller E. Comparison and correlation of Neisseria meningitidis serogroup B immunological assays and human antibody responses following three doses of the ‘Norwegian’ meningococcal outer membrane vesicle vaccine, MenBvac. Infect Immun. 2006;74:4557–4565. doi: 10.1128/IAI.00466-06.
    1. Blanchard-Rohner G, Watt H, Kelly DF, Yu LM, Snape MD, Pollard AJ. Baseline polysaccharide-specific antibodies may not consistently inhibit booster antibody responses in infants to a serogroup C meningococcal protein-polysaccharide conjugate vaccine. Vaccine. 2012;30:4153–4159. doi: 10.1016/j.vaccine.2012.04.063.
    1. Jokhdar H, Borrow R, Sultan A, Adi M, Riley C, Fuller E, Baxter D. Immunological hyporesponsiveness to group C but not group A following repeated meningococcal A/C polysaccharide vaccination in Saudi Arabia. Clin Diagn Lab Immunol. 2004;11:83–88.
    1. Keyserling H, Papa T, Koranyi K, Ryall R, Bassily E, Bybel MJ, Sullivan K, Gilment G, Reinhardt A. Safety, immunogenicity and immune memory of a novel meningococcal (groups A, C, Y and W135) polysaccharide diptheria toxoid conjugate vaccine (MCV-4) in health adolescents. Arch Pediatr Adolesc Med. 2005;159:907–913. doi: 10.1001/archpedi.159.10.907.
    1. Granoff DM, Gupta RK, Belshe RB, Anderson EL. Induction of immunological refractoriness in adults by meningococcal C polysaccharide vaccination. J Infect Dis. 1998;178:870–874. doi: 10.1086/515346.
    1. Richmond P, Kaczmarski E, Borrow R, Findlow J, Clark S, McCann R, Hill J, Barker M, Miller E. Meningococcal C polysaccharide vaccine induces immunological hyporesponsiveness in adults that is overcome by meningococcal C conjugate vaccine. J Infect Dis. 2000;181:761–764. doi: 10.1086/315284.
    1. Gold R, Lepow ML, Goldschneider I, Draper T, Gotschlich EC. Clinical evaluation of group A and C meningococcal polysaccharide vaccine in infants. J Clin Invest. 1975;56:1536–1547. doi: 10.1172/JCI108235.
    1. MacDonald NE, Halperin SA, Law BJ, Forrest B, Danzig L, Granoff DM. Induction of immunologic memory by conjugated vs. plain meningococcal C polysaccharide vaccine in toddlers. JAMA. 1998;280:1685–1689. doi: 10.1001/jama.280.19.1685.
    1. Findlow H, Sow S, Borrow R, Tapia M, Haidara FC, Akinsola AK, Idoko OT, Diallo F, Adegbola R, Tang Y, Parulekar V, Chadha H, Mabey L, Holme D, Townsend K, Chaumont J, LaForce FM, Kulkarni PA, Marchetti E, Viviani S, Hassan-King M, Preziosi MP. Meningococcal group C and W135 immunological hyporesponsiveness in African toddlers. Clin Vaccine Immunol. 2011;18:1492–1496. doi: 10.1128/CVI.05020-11.
    1. Southern J, Deane S, Ashton L, Borrow R, Goldblatt D, Andrews N, Balmer P, Morris R, Kroll JS, Miller E. Effects of prior polysaccharide vaccination on magnitude, duration, and quality of immune responses to and safety profile of a meningococcal serogroup C tetanus toxoid conjugate vaccination in adults. Clin Diagn Lab Immunol. 2004;11:1100–1104.
    1. Ladhani S, Ramsay M, Flood J, Campbell H, Slack M, Pebody R, Findlow J, Newton E, Wilding M, Warrington R, Crawford H, Min S, Gray K, Martin S, Frankland S, Bokuvha N, Laher G, Borrow R. Haemophilus influenzae serotype B (Hib) seroprevalence in England and Wales in 2009. Euro Surveill. 2012;17(46)
    1. Wagner KS, White JM, Andrews N, Borrow R, Stanford E, Newton E, Pebody RG. Immunity to tetanus and diphtheria in the UK in 2009. Vaccine. 2012;30:7111–7117. doi: 10.1016/j.vaccine.2012.09.029.
    1. Burrage M, Robinson A, Borrow R, Andrews N, Southern J, Findlow J, Martin S, Thornton C, Goldbaltt D, Corbel M, Sesardic D, Cartwright K, Richmond P, Miller E. Effect of vaccination with carrier protein on response to meningococcal C conjugate vaccines and value of different immunoassays as predictors of protection. Infect Immun. 2002;70:4946–4954. doi: 10.1128/IAI.70.9.4946-4954.2002.
    1. Kshirsagar N, Mur N, Thatte U, Gogtay N, Viviani S, Preziosi MP, Elie C, Findlow H, Carloen G, Borrow R, Parulekar V, Plikaytis B, Kulkarni P, Imbault N, LaForce M. Safety, immunogenicity, and antibody persistence of a new meningococcal group A conjugate vaccine in health Indian adults. Vaccine. 2007;25S:A101–A107.
    1. Miller JM, Mesaros N, Van Der Wielen M, Baine Y. Conjugate meningococcal vaccines development: GSK Biologicals experience. Adv Prev Med. 2011. 10.4061/2011/846756.
    1. Perrett KP, Winter AP, Kibwana E, Jin C, John TM, Yu LM, Borrow R, Curtis N, Pollard AJ. Antibody persistence after serogroup C meningococcal conjugate immunisation of United Kingdom primary-school children in 1999–2000 and responses to a booster: a phase 4 clinical trial. Clin Infect Dis. 2010;50:1601–1610. doi: 10.1086/652765.

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera