An 18-month-old, partially vaccinated boy is brought to the office for a routine well-child examination. His parents have elected a delayed schedule for vaccine administration based on personal preferences. Today, the patient is scheduled to receive the Haemophilus influenzae serotype b (Hib) conjugate vaccine. The parents are given detailed information about the vaccine, but the mother asks, "Why is 'tetanus toxoid conjugate' listed on the package insert?" She adds that her son already received the diphtheria-tetanus-acellular pertussis (DTaP) vaccine. The parents request an explanation for the reason the Hib vaccine contains both the capsular polysaccharide of Hib as well as the conjugated tetanus toxoid. Which of the following best describes the purpose of Hib vaccine conjugation?
Immunogenicity of polysaccharide vs conjugate vaccines | ||
Immunology | Polysaccharide vaccine | Polysaccharide-protein conjugate vaccine |
Response type | B cell | B cell & T cell |
Memory cell response | No | Yes |
Relative duration of immunity | Short | Long |
Immunogenicity in infancy | No | Yes |
Haemophilus influenzae serotype b (Hib), an encapsulated gram-negative coccobacillus, was previously a common, invasive, and potentially fatal cause of pneumonia, epiglottitis, and meningitis in children. Neonates are protected with maternal anti-Hib IgG antibodies from placental transfer in utero, but this protection wanes as the immunoglobulins are degraded during the first few months of life. Therefore, widespread vaccination with the Hib polysaccharide-protein conjugate vaccine series is recommended starting at age 2 months; this practice has dramatically reduced the incidence of Hib infection.
Bacteria with polysaccharide capsules (eg, Hib, Streptococcus pneumoniae [pneumococcus], Neisseria meningitidis) are antiphagocytic. The polysaccharide capsule provokes an antibody-mediated (B cell) immune response and is the primary antigenic constituent of vaccines against encapsulated bacteria. However, vaccines containing the polysaccharide antigen alone are ineffective in children age <2 years due to their immature humoral immunity. Therefore, the polysaccharide is conjugated with a carrier protein to amplify the patient's humoral response against the polysaccharide through T cell recruitment. The Hib conjugate vaccine contains a carrier protein that is derived from either a tetanus toxoid (TT) protein or an outer membrane protein (OMP) of Neisseria meningitidis. The polysaccharide-protein conjugate then becomes a T cell-dependent antigen. Immunogenicity is increased as a result of T cell-dependent stimulation of B lymphocytes and the production of memory B lymphocytes.
(Choice A) Conjugation does not affect vaccine safety. The main adverse effects of the Hib vaccine include fever, irritability, and injection site reactions (eg, pain, redness, swelling).
(Choice C) Although conjugation allows for a more robust immune response, a 2- or 3-dose primary series in infancy followed by a booster dose is still required to achieve protective Hib antibody levels.
(Choice D) Nontypeable H influenzae represents nonencapsulated strains that generally cause local disease (eg, sinusitis, otitis media). These bacteria colonize the nasopharynx of most individuals age >5 years. The Hib vaccine does not confer protection against nontypeable H influenzae.
(Choice E) Conjugated OMP and TT protein do not elicit protective antibody levels. Therefore, a patient is not considered to be immunized against the pathogen that the carrier protein is derived from.
Educational objective:
The Haemophilus influenzae serotype b vaccine consists of a capsular polysaccharide conjugated to a carrier protein (tetanus toxoid [TT] protein or outer membrane protein [OMP] of Neisseria meningitidis). Protein conjugation causes a T cell-mediated immune response leading to long-term immunity through production of memory B-lymphocytes.