Immunologic interference from sequential administration of live attenuated alphavirus vaccines

Area of Science:

• Virology
• Immunology
• Vaccinology

Background:

• Alphaviruses, including VEEV and CHIKV, pose significant public health threats.
• Sequential vaccination strategies are increasingly employed for broad pathogen protection.
• Interference between vaccines targeting related viruses requires thorough investigation.

Purpose of the Study:

• To investigate the impact of prior Venezuelan equine encephalitis virus (VEEV) vaccination on immune responses to a chikungunya virus (CHIKV) vaccine.
• To evaluate the neutralizing antibody responses to a live attenuated VEEV vaccine following prior CHIKV vaccination or placebo.
• To assess potential cross-reactivity and anamnestic antibody responses in sequential alphavirus vaccination.

Main Methods:

• Two human vaccine trials were conducted to assess sequential administration of VEEV and CHIKV vaccines.
• Neutralizing antibody responses were measured using plaque-reduction neutralization tests (PRNT).
• Enzyme-linked immunosorbent assays (ELISA) were used to detect cross-reactive IgG antibodies.

Main Results:

• Previous VEEV vaccination led to a low response rate (46%) to a live attenuated CHIKV vaccine.
• CHIKV vaccine recipients showed significantly lower VEEV neutralizing antibody titers (GMT < 10) compared to VEEV-naive controls (GMT 95) (P < .003).
• ELISA revealed cross-reactive IgG to VEEV after CHIKV immunization, followed by an anamnestic response upon VEEV vaccination.

Conclusions:

• Preexisting immunity to one alphavirus interferes with the immune response to a subsequent, heterologous alphavirus vaccine in humans.
• This interference affects both neutralizing antibody production and vaccine efficacy.
• Understanding and mitigating vaccine interference is crucial for optimizing sequential vaccination schedules.