Evaluation of the Induction of Immune Memory Following Infant Immunisation with Serogroup C Neisseria Meningitidis Conjugate Vaccines--exploratory Analyses Within a Randomised Controlled Trial

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2014 Jul 15

PMID 25020050

Citations 4

Authors

Ameneh Khatami

Elizabeth A Clutterbuck

Amber J Thompson

Jennifer A McKenna

David Pace

Jacqueline Birks

Matthew D Snape

Andrew J Pollard

Affiliations

Soon will be listed here.

Abstract

Aim: We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory.

Methods: Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age.

Results: Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children.

Conclusions: MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.

Trial Registration: EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.

Citing Articles

Human B Cell Responses to Dominant and Subdominant Antigens Induced by a Meningococcal Outer Membrane Vesicle Vaccine in a Phase I Trial.

Rollier C, Dold C, Marsay L, Linder A, Green C, Sadarangani M mSphere. 2022; 7(1):e0067421.

PMID: 35080470 PMC: 8791392. DOI: 10.1128/msphere.00674-21.

Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine.

Fuery A, Richmond P, Currie A PLoS One. 2015; 10(7):e0133126.

PMID: 26191794 PMC: 4507978. DOI: 10.1371/journal.pone.0133126.

Is a single infant priming dose of meningococcal serogroup C conjugate vaccine in the United Kingdom sufficient?.

Findlow H, Borrow R Hum Vaccin Immunother. 2015; 11(6):1501-6.

PMID: 25912095 PMC: 4514293. DOI: 10.1080/21645515.2015.1019189.

Immunogenicity of reduced dose priming schedules of serogroup C meningococcal conjugate vaccine followed by booster at 12 months in infants: open label randomised controlled trial.

Pace D, Khatami A, McKenna J, Campbell D, Attard-Montalto S, Birks J BMJ. 2015; 350:h1554.

PMID: 25832102 PMC: 4382115. DOI: 10.1136/bmj.h1554.

References

Borrow R, Goldblatt D, Finn A, Southern J, Ashton L, Andrews N . Immunogenicity of, and immunologic memory to, a reduced primary schedule of meningococcal C-tetanus toxoid conjugate vaccine in infants in the United kingdom. Infect Immun. 2003; 71(10):5549-55. PMC: 201087. DOI: 10.1128/IAI.71.10.5549-5555.2003. View

Kelly D, Snape M, Clutterbuck E, Cutterbuck E, Green S, Snowden C . CRM197-conjugated serogroup C meningococcal capsular polysaccharide, but not the native polysaccharide, induces persistent antigen-specific memory B cells. Blood. 2006; 108(8):2642-7. DOI: 10.1182/blood-2006-01-009282. View

Clutterbuck E, Oh S, Hamaluba M, Westcar S, Beverley P, Pollard A . Serotype-specific and age-dependent generation of pneumococcal polysaccharide-specific memory B-cell and antibody responses to immunization with a pneumococcal conjugate vaccine. Clin Vaccine Immunol. 2007; 15(2):182-93. PMC: 2238039. DOI: 10.1128/CVI.00336-07. View

Borrow R, Balmer P, Miller E . Meningococcal surrogates of protection--serum bactericidal antibody activity. Vaccine. 2005; 23(17-18):2222-7. DOI: 10.1016/j.vaccine.2005.01.051. View

Khatami A, Snape M, John T, Westcar S, Klinger C, Rollinson L . Persistence of immunity following a booster dose of Haemophilus influenzae type B-Meningococcal serogroup C glycoconjugate vaccine: follow-up of a randomized controlled trial. Pediatr Infect Dis J. 2010; 30(3):197-202. DOI: 10.1097/INF.0b013e3181f728fd. View

Granoff D, Pollard A . Reconsideration of the use of meningococcal polysaccharide vaccine. Pediatr Infect Dis J. 2007; 26(8):716-22. DOI: 10.1097/INF.0b013e3180cc2c25. View

Pace D, Snape M, Westcar S, Oluwalana C, Yu L, Begg N . A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose for toddlers: a phase 3 open randomised controlled trial. Arch Dis Child. 2008; 93(11):963-70. DOI: 10.1136/adc.2007.136036. View

Hawkins E, Turner M, Dowling M, van Gend C, Hodgkin P . A model of immune regulation as a consequence of randomized lymphocyte division and death times. Proc Natl Acad Sci U S A. 2007; 104(12):5032-7. PMC: 1821128. DOI: 10.1073/pnas.0700026104. View

Caugant D, Tzanakaki G, Kriz P . Lessons from meningococcal carriage studies. FEMS Microbiol Rev. 2007; 31(1):52-63. DOI: 10.1111/j.1574-6976.2006.00052.x. View

10.

Blink E, Light A, Kallies A, Nutt S, Hodgkin P, Tarlinton D . Early appearance of germinal center-derived memory B cells and plasma cells in blood after primary immunization. J Exp Med. 2005; 201(4):545-54. PMC: 2213050. DOI: 10.1084/jem.20042060. View

11.

Kelly D, Snape M, Perrett K, Clutterbuck E, Lewis S, Blanchard Rohner G . Plasma and memory B-cell kinetics in infants following a primary schedule of CRM 197-conjugated serogroup C meningococcal polysaccharide vaccine. Immunology. 2009; 127(1):134-43. PMC: 2678189. DOI: 10.1111/j.1365-2567.2008.02934.x. View

12.

Andrews N, Borrow R, Miller E . Validation of serological correlate of protection for meningococcal C conjugate vaccine by using efficacy estimates from postlicensure surveillance in England. Clin Diagn Lab Immunol. 2003; 10(5):780-6. PMC: 193909. DOI: 10.1128/cdli.10.5.780-786.2003. View

13.

Alugupalli K, Leong J, Woodland R, Muramatsu M, Honjo T, Gerstein R . B1b lymphocytes confer T cell-independent long-lasting immunity. Immunity. 2004; 21(3):379-90. DOI: 10.1016/j.immuni.2004.06.019. View

14.

Richmond P, Borrow R, Goldblatt D, Findlow J, Martin S, Morris R . Ability of 3 different meningococcal C conjugate vaccines to induce immunologic memory after a single dose in UK toddlers. J Infect Dis. 2000; 183(1):160-3. DOI: 10.1086/317646. View

15.

Vora K, Manser T . Contrasting the in situ behavior of a memory B cell clone during primary and secondary immune responses. J Immunol. 1999; 163(8):4315-27. View

16.

Goldblatt D, Southern J, Ashton L, Richmond P, Burbidge P, Tasevska J . Immunogenicity and boosting after a reduced number of doses of a pneumococcal conjugate vaccine in infants and toddlers. Pediatr Infect Dis J. 2006; 25(4):312-9. DOI: 10.1097/01.inf.0000207483.60267.e7. View

17.

Russell F, Licciardi P, Balloch A, Biaukula V, Tikoduadua L, Carapetis J . Safety and immunogenicity of the 23-valent pneumococcal polysaccharide vaccine at 12 months of age, following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine in infancy. Vaccine. 2010; 28(18):3086-94. PMC: 2857918. DOI: 10.1016/j.vaccine.2010.02.065. View

18.

Khatami A, Snape M, Ohene-Kena B, Young K, Oeser C, Michaelis L . Phase II study of a three-dose primary vaccination course of DTPa-IPV/Hib-MenC-TT followed by a 12-month Hib-MenC-TT booster in healthy infants. Pediatr Infect Dis J. 2013; 32(6):675-81. DOI: 10.1097/INF.0b013e31828672a7. View

19.

Blanchard Rohner G, Snape M, Kelly D, John T, Morant A, Yu L . The magnitude of the antibody and memory B cell responses during priming with a protein-polysaccharide conjugate vaccine in human infants is associated with the persistence of antibody and the intensity of booster response. J Immunol. 2008; 180(4):2165-73. DOI: 10.4049/jimmunol.180.4.2165. View

20.

Maurer D, Fischer G, Fae I, Majdic O, Stuhlmeier K, von Jeney N . IgM and IgG but not cytokine secretion is restricted to the CD27+ B lymphocyte subset. J Immunol. 1992; 148(12):3700-5. View