What causes the inability to create an adequate antibody titer after Varicella (chickenpox) vaccination?

From the Guidelines

The inability to create an adequate antibody titer after varicella vaccination is primarily caused by primary vaccine failure, which can be attributed to various factors, including immunodeficiency conditions, advanced age, improper vaccine storage or administration, and genetic factors affecting individual immune responses. According to the study by 1, after 1 dose of monovalent varicella vaccine, 76% of healthy children seroconvert, as measured by FAMA assay, suggesting that many breakthrough cases of varicella in children who have received 1 dose of varicella vaccine may be attributable to primary vaccine failure rather than waning immunity.

Factors Contributing to Inadequate Antibody Titer

• Immunodeficiency conditions, such as HIV/AIDS, cancer treatments, or congenital immune disorders
• Advanced age, which naturally reduces immune response
• Improper vaccine storage or administration
• Genetic factors affecting individual immune responses
• Certain medications, such as high-dose corticosteroids (prednisone >20mg daily for >2 weeks), immunosuppressants (tacrolimus, cyclosporine), and some biologics (rituximab, infliximab)
• Malnutrition, particularly protein deficiency, can compromise antibody production

Recommendations for Patients with Inadequate Titers

• Revaccination may be recommended, typically with the standard two-dose regimen of Varivax or Varilrix administered 4-8 weeks apart, as supported by the study 1, which shows that a second dose of varicella vaccine can provide improved protection to the 15%--20% of children who do not respond adequately to the first dose.
• In cases of persistent inadequate response, particularly in immunocompromised individuals, passive immunization with VariZIG (varicella zoster immune globulin) may be necessary for post-exposure prophylaxis, as the immune response to vaccines requires proper antigen presentation, T-cell activation, and B-cell antibody production - any disruption in this cascade can result in suboptimal antibody titers. The study 1 highlights the importance of humoral and cellular immunity in viral clearance and protection against reinfection or reactivation of latent VZV.

From the Research

Causes of Inability to Create an Adequate Antibody Titer after Varicella Vaccination

• The inability to create an adequate antibody titer after varicella vaccination can be caused by several factors, including the type of vaccine used and the individual's immune response 2.
• Some individuals may have a low antibody response to the VZV vaccine despite an adequate cell-mediated response, making it difficult to achieve an adequate antibody titer 2.
• The virus titer of the varicella vaccine can also affect the ability to create an adequate antibody titer, with lower virus titers resulting in decreased immunogenicity 3.
• In some cases, the antibody titer may decrease over time, even after initial seroconversion, making it necessary for repeated vaccinations to maintain adequate protection 4.
• Certain individuals, such as those with impaired cellular immunity, may have difficulty creating an adequate antibody titer after varicella vaccination 5.
• The timing of additional vaccinations can also impact the ability to create an adequate antibody titer, with booster vaccinations given 3-5 years after the initial vaccination showing greater immunogenicity 6.

Factors Affecting Antibody Titer

• The type of assay used to measure antibody titer can affect the results, with some assays being more sensitive than others 2.
• The individual's immune status, including the presence of immunosuppression, can impact the ability to create an adequate antibody titer 4.
• The presence of underlying medical conditions, such as developmental retardation, can also affect the immune response to varicella vaccination 5.

Implications for Vaccination Strategies

• The results of these studies suggest that repeated vaccinations may be necessary to maintain adequate protection against varicella, particularly in certain individuals such as those with impaired cellular immunity 4, 6.
• The use of more sensitive assays to measure antibody titer may be necessary to accurately assess the immune response to varicella vaccination 2.
• Further research is needed to determine the optimal vaccination strategy for individuals with impaired immune function or other underlying medical conditions 5.