Is there a protective titer for Meningococcal Conjugate Vaccine (MCV4)?

From the Guidelines

There is no universally accepted protective antibody titer for Meningococcal Conjugate Vaccine (MCV4). Unlike some vaccines where specific antibody levels correlate with protection, meningococcal immunity is more complex and involves multiple immunological mechanisms. Serum bactericidal antibody (SBA) assays with human complement are considered the best correlate of protection, with titers ≥1:4 generally associated with protection against meningococcal disease 1. However, these assays are primarily used in research settings rather than routine clinical practice. For this reason, protection is determined by vaccination status rather than antibody titers.

The Advisory Committee on Immunization Practices recommends MCV4 for adolescents at age 11-12 with a booster at age 16, and for high-risk individuals including those with complement deficiencies, asplenia, or HIV. For high-risk patients, revaccination every 5 years is recommended if the risk remains 1. The absence of a clinically useful protective titer means that adherence to vaccination schedules is the primary way to ensure protection against meningococcal disease. Key points to consider include:

• The decline in bactericidal antibody titers over time, with geometric mean antibody titers (GMTs) declining by as much as 90% over 3 years for serogroup C 1
• The proportion of adolescents vaccinated at age 11 years with MenACWY-D determined to have protective antibodies 3 years later was 71%–95% 1
• The importance of revaccination every 5 years for high-risk patients to maintain protection against meningococcal disease 1

From the Research

Meningococcal Conjugate Vaccine (MCV4) Titer

• The concept of a protective titer for MCV4 is closely related to serum bactericidal antibody (SBA) activity, which is a widely accepted surrogate of protection against meningococcal disease 2, 3.
• For serogroup C, an SBA titer of either ≥4 or ≥8 has been utilized to indicate protection, depending on whether human or baby rabbit complement is used, respectively 2.
• Studies have shown that post-licensure effectiveness data for serogroup C conjugate vaccines support the acceptance of rSBA titers ≥8 as the correlate of protection for this serogroup 3.
• However, for serogroups A, W, and Y, no formal thresholds have been established 3.
• Research on MenACWY-TT immunogenicity has used both hSBA and rSBA assays, suggesting that rSBA may be more appropriate for these measurements 3.
• A study on the validation of serological correlates of protection for meningococcal C conjugate vaccine found that rSBA cutoffs of ≥4 or ≥8 at 4 weeks post-vaccination were consistent with observed efficacy 4.
• Another study compared the safety and immunogenicity of quadrivalent (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine (MCV-4) versus quadrivalent polysaccharide vaccine in children, and found that MCV-4 elicited significantly higher and more persistent serum bactericidal antibody responses against meningococcal serogroups A, C, Y, and W-135 5.

Key Findings

• SBA activity is a key correlate of protection for meningococcal disease 2, 3, 6.
• Different SBA titers may be used to indicate protection, depending on the serogroup and complement source used 2, 3.
• Further research is needed to establish formal thresholds for serogroups A, W, and Y 3.
• MCV-4 has been shown to elicit significant immune responses against meningococcal serogroups A, C, Y, and W-135 5.