Humoral immune responses to a protective peptide-conjugate against measles after different prime-boost regimens

Area of Science:

• Immunology
• Vaccinology
• Virology

Background:

• Current live-attenuated measles vaccines (MV) leave infants vulnerable until the recommended vaccination age.
• A previously identified measles virus hemagglutinin noose epitope (HNE) peptide can induce virus-neutralizing antibodies.

Purpose of the Study:

• To investigate the immunogenicity and protective potential of HNE peptide-conjugates with diphtheria or tetanus toxoids.
• To evaluate the impact of active and passive immune priming on the response to these peptide-conjugates.

Main Methods:

• Mice were immunized with HNE peptide-conjugates of diphtheria or tetanus toxoid.
• Mice were also subjected to active or passive priming with antibodies against the peptide, toxoids, or conjugates.
• Immunogenicity was assessed by antibody titers, cross-reactivity with MV, and protection against lethal MV challenge.

Main Results:

• Both HNE peptide-conjugates induced high titers of peptide antibodies that cross-reacted with MV.
• Conjugates provided protection against a lethal intracranial challenge with a rodent-adapted MV, even after prior immunization with toxoids or conjugates.
• Diphtheria toxoid carriers were less susceptible to peptide-specific epitopic suppression than tetanus toxoid carriers, and suppression could be overcome by an additional boost.

Conclusions:

• HNE peptide-conjugates are immunogenic and protective against measles virus challenge.
• These peptide-based conjugates show potential as early infant vaccine candidates to bridge the protection gap.
• Early conjugate vaccination does not interfere with subsequent response to the live-attenuated MV vaccine.