What is the most likely explanation for the failure of a group with a specific Human Leukocyte Antigen (HLA) type to respond to immunization with a recombinant polypeptide vaccine?

From the Guidelines

The most likely explanation for the failure of a group with a specific Human Leukocyte Antigen (HLA) type to respond to immunization with a recombinant polypeptide vaccine is that the vaccine's antigenic epitopes are not effectively presented by that particular HLA type. HLA molecules are crucial for presenting foreign antigens to T cells, which is essential for mounting an effective immune response. Different HLA types have varying binding affinities for different peptide sequences. If the vaccine's polypeptide contains epitopes that cannot be efficiently bound and presented by a specific HLA type, individuals with that HLA type will not generate a robust T cell response following vaccination. This phenomenon, known as HLA restriction, explains why vaccine efficacy can vary across populations with different genetic backgrounds, as seen in the COVID-19 pandemic where certain HLA types, such as HLA-B*46:01, were found to be more vulnerable to the disease 1. Vaccine developers should consider HLA polymorphism during design by including multiple epitopes that can be presented by diverse HLA types, ensuring broader population coverage. Some key points to consider include:

• HLA molecules play a critical role in presenting antigens to T cells
• Different HLA types have varying binding affinities for different peptide sequences
• HLA restriction can lead to varying vaccine efficacy across different populations
• Considering HLA polymorphism during vaccine design can help achieve broader population coverage Additionally, alternative vaccine formulations or adjuvants might be necessary for individuals with non-responsive HLA types to achieve protective immunity. Understanding the role of HLA in immune response, as highlighted by the use of public health genomics during the COVID-19 pandemic 1, can inform strategies to improve vaccine efficacy and protect vulnerable populations.

From the Research

Failure to Respond to Immunization

The failure of a group with a specific Human Leukocyte Antigen (HLA) type to respond to immunization with a recombinant polypeptide vaccine can be attributed to several factors.

• The association between HLA alleles and immune response to vaccines has been studied extensively 2, 3, 4.
• Research has shown that certain HLA alleles can influence the ability of an individual to mount an immune response to specific vaccines, such as the influenza vaccine 2 and the measles vaccine 3, 4.
• For example, the HLA-DRB1*0701 allele has been associated with nonresponsiveness to influenza virus vaccination 2, while certain HLA-B alleles have been linked to nonresponse or hyper-response to the measles vaccine 3, 4.
• The mechanism behind this association is thought to involve the recognition of antigens by CD4+ T cells in association with HLA class II molecules, which can affect the neutralizing antibody response to the vaccine 2.
• Additionally, the concept of using HLA allele selection for designing peptide vaccines has been explored, with the goal of achieving a prespecified coverage of a population 5.

HLA Alleles and Vaccine Response

The specific HLA allele associated with nonresponse to the recombinant polypeptide vaccine is not specified, but it is likely that this allele affects the ability of CD4+ T cells to recognize and respond to the vaccine antigen.

• The study of HLA alleles and their association with vaccine response can provide valuable insights into the development of more effective vaccines 3, 4.
• Further research is needed to fully understand the relationship between HLA alleles and immune response to vaccines, and to develop strategies for overcoming nonresponse in individuals with specific HLA types 2, 5.