Vaccine Failure After Meningococcal C Conjugate Vaccine May Be Linked to Decline of Bactericidal Titers and Absence of Herd Immunity

To the Editors:

We read with interest the article by Perrett et al¹ describing antibody persistence in Australian adolescents after meningococcal C conjugate (MenC) vaccination. Among the children who received a single catch-up dose of MenC vaccine (2–8 years old), only 34% of healthy adolescents showed ≥4 titers of human serum antibactericidal antibody (hSBA) (titer correlates of protection). Moreover, serum bactericidal antibody assay with rabbit complement titers (both proportions of subjects achieving rabbit serum bactericidal antibody of ≥8 and the geometric mean rabbit serum bactericidal antibody) declined faster when the age of vaccination was earlier. The impact of this decline may be amplified if the immunization coverage is insufficient. Cases of vaccine failure occur, as was shown by surveillance data follow-up of MenC vaccines introduced in the United Kingdom at the implementation of the vaccination program.²

In France in 2009, a single MenC vaccination was recommended for children 1–2 years old, with an extended catch-up to 24 years of age. Due to the lack of involvement of the French health authority to promote this vaccine, the vaccine coverage remains very low in France for implantation of the vaccination strategy. By the end of 2013, only 50% among children 1–4 years, 13% among adolescents of 15–19 years and 3% among adults of 20–24 years were vaccinated.³ Here, we describe 2 cases of vaccine failure since 2010, after MenC vaccine implementation in France.

A previously healthy 5-year-old boy who received MenC-CRM vaccine (Meningitec; Wyeth Vaccines, UK) at 14 months of age presented to our pediatric department in October 2014 with a 48-hour history of fever, headache and vomiting. He had no identified hemodynamic dysfunction. Physical examination revealed neck rigidity with Kernig’s and Brudzinski’s signs. No focal signs or purpura was observed. Analysis of cerebrospinal fluid (CSF) revealed 30 white blood cells/µL (94% neutrophils), 50 red blood cells/µL, 16 mg/dL protein and 79 mg/dL glucose. Microscopy and culture of blood and CSF showed no organisms. Blood and CSF polymerase chain reaction testing for serogroup C meningococcal DNA were positive. The patient was discharged after a 7-day course of cefotaxime. Total hemolytic complement (CH50), C3, C4 and properdin values were normal. Analysis of hSBA revealed the absence of protective titers (<4) at admission and on day 15. However, the titers increased slightly at day 45 postinfection and highly at 1 month after the second vaccination (8 and 128, respectively), with MenC-TT (NeisVac-C; currently marketed by Pfizer, New York) suggesting that this child responded to vaccination.

The second case of vaccine failure was a previously healthy 7-year-old girl who had received MenC-TT (NeisVac-C; Baxter Healthcare) at 13 months of age and was admitted to the pediatric department of Lisieux in July 2011 because of signs of meningeal irritation. She had received cefixime for 7 days before the admission. In the emergency department, the patient was febrile, with no skin anomalies or signs of shock. CSF analysis revealed a white blood cell count of 400 cells/mm³ (89% neutrophils) with normal glucose (59.4 mg/dL) and protein (27 mg/dL) concentrations. Microscopy and culture of blood and CSF showed no organisms. CSF was positive for serogroup C Neisseria meningitidis by polymerase chain reaction. The patient was discharged after a 7-day course of cefotaxime. Total hemolytic complement (CH50) and C3 values were normal, and hSBA titers were <4 at admission and on day 17.

Auckland et al⁴ showed that after 1.8–44 months of the introduction of MenC vaccine, hSBA titers in convalescent serum samples (median 32 days since onset) and the avidity index of antibodies in acute serum were significantly higher in vaccine failure cases than in unvaccinated cases. We found no cases of vaccine failure after 4 years of age based on serologic testing in response to MenC disease in the literature. The annual number of vaccine failure cases has greatly decreased at 8 years after the introduction of MenC vaccine, and few have occurred 5 years after completion of the primary vaccination.⁵ Several studies have shown inadequate serologic protection against MenC (>18 months after MenC vaccine), and the persistence of MenC immunity and response to booster dose depends on age at priming.^6,7

The decline of bactericidal titer after vaccination at 14 months of age (4 and 6 years before the current infections for cases 1 and 2, respectively) is most likely responsible for their susceptibility to the infection. Meningococcal isolates are still circulating in France as suggested by the increase in the incidence of nonvaccinated subjects (mainly under 1 year).³ In agreement with the data presented by Perrett et al,¹ low vaccine coverage combined with the decline in serum bactericidal titers predict the occurrence of vaccine failure cases. Revisiting the vaccination strategy against meningococci serogroup C in France seems warranted. Enhancing vaccination uptake/compliance among adolescents should be a priority. A booster dose at the age of 11–13 years is one possibility to strengthen herd immunity among these subjects where most meningococcal disease occurs.

Rania Matar, MD

Service de pédiatrie générale

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Eva Hong, MD

Institut Pasteur

Invasive Bacterial Infections Unit

National Reference Center for Meningococci

Paris, France

Corinne Levy, MD

GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie)

ACTIV (Association Clinique et Thérapeutique Infantile du Val de Marne)

Paris, France

CRC-CHI Créteil

Créteil, France

Marcel Guillot, MD

Service de pédiatrie générale

Centre Hospitalier de Lisieux

Lisieux, France

Robert Cohen, MD

GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie)

ACTIV (Association Clinique et Thérapeutique Infantile du Val de Marne)

Paris, France

Service de Néonatologie

Centre Hospitalier Intercommunal de Créteil

Créteil, France

Muhamed-Kheir Taha, PhD, MD

Institut Pasteur

Invasive Bacterial Infections Unit

National Reference Center for Meningococci

Paris, France

Fouad Madhi, MD

Service de pédiatrie générale

Centre Hospitalier Intercommunal de Créteil

Créteil, France

GPIP (Groupe de Pathologie Infectieuse Pédiatrique) de la SFP (Société Française de Pédiatrie)

Paris, France