Conjugate Meningococcal Vaccines (MenACWY)
Conjugate meningococcal vaccines (MenACWY) are vaccines in which meningococcal capsular polysaccharides from serogroups A, C, W, and Y are covalently coupled (conjugated) to a protein carrier, transforming the immune response from T-lymphocyte-independent to T-lymphocyte-dependent, resulting in improved immunogenicity in infants and creation of immunologic memory. 1
Mechanism and Immunologic Advantage
The conjugation process fundamentally changes how the immune system responds to the vaccine:
Conjugation links the polysaccharide antigen to a protein carrier containing T-lymphocyte epitopes, converting the immune response from T-lymphocyte-independent (seen with plain polysaccharide vaccines) to T-lymphocyte-dependent 1
This results in improved primary antibody responses, especially in children under 2 years of age, a population in which plain polysaccharide vaccines are poorly immunogenic 1
Conjugate vaccines induce stronger anamnestic (memory) responses upon reexposure to the pathogen, providing longer-lasting protection compared to polysaccharide-only vaccines 1
Protection against invasive meningococcal disease is mediated by serum bactericidal antibodies, which serve as the immunologic surrogate of protection 1
FDA-Licensed Conjugate Vaccines in the United States
Three meningococcal conjugate vaccines have been licensed by the FDA:
MenACWY-D (Menactra)
- Licensed in January 2005 by Sanofi Pasteur 1
- Contains 4 μg each of capsular polysaccharide from serogroups A, C, Y, and W conjugated to approximately 48 μg of diphtheria toxoid 1, 2
- Approved as a single dose for persons aged 2 through 55 years and as a 2-dose series in children aged 9 through 23 months 1
- Administered as an intramuscular injection 1
MenACWY-CRM (Menveo)
- Licensed in February 2010 by Novartis Vaccines 1
- Contains 10 μg of capsular polysaccharide from serogroup A and 5 μg each from serogroups C, Y, and W conjugated to CRM197 (a nontoxic form of diphtheria toxin) 1
- Approved as a single dose for persons aged 2 through 55 years 1
- Requires reconstitution of lyophilized serogroup A component with liquid C, Y, and W components before administration 1
- Administered as an intramuscular injection, preferably into the deltoid region 1
Hib-MenCY-TT (MenHibrix)
- Licensed by GlaxoSmithKline as a bivalent vaccine containing serogroups C and Y conjugated to tetanus toxoid, also providing protection against Haemophilus influenzae type b 1
Comparison to Polysaccharide Vaccines
Conjugate vaccines are strongly preferred over the older quadrivalent meningococcal polysaccharide vaccine (MPSV4, Menomune) for persons aged 2-55 years 1:
- MPSV4 induces a T-lymphocyte-independent immune response with limited immunologic memory and poor responses in young children 2
- MPSV4 does not substantially reduce nasopharyngeal carriage or interrupt transmission, failing to elicit herd immunity 2
- Multiple doses of polysaccharide vaccines may cause immunologic hyporesponsiveness to serogroups A and C, a phenomenon not seen with conjugate vaccines 2
Clinical Efficacy Evidence
Effectiveness of conjugate vaccines was inferred by comparing serum bactericidal antibody (SBA) measurements with the U.S.-licensed standard of care vaccine among persons aged 2-55 years 1
In adolescents aged 11-18 years, MenACWY-CRM demonstrated noninferiority to MenACWY-D for all four serogroups, with statistically higher antibody responses for serogroups A, W, and Y, though the clinical relevance of higher responses is unknown 1
Safety and reactogenicity profiles are comparable between different conjugate vaccine formulations 1
Newer Formulations
Additional conjugate vaccines have been developed more recently: