Protection from Lyme neuroborreliosis in nonhuman primates with a multiantigenic vaccine.
In an effort to develop an effective and safe vaccine for lyme disease, rhesus macaques were injected with a multiantigenic preparation of Borrelia burgdorferi, strain N40. One month later animals were boosted before intradermal challenge with infectious B. burgdorferi. Challenges were performed at 1 and again at 5 months after the booster vaccination. Vaccinated and control nonvaccinated animals were monitored for development of systemic infection by measurement of serum anti-spirochetal antibodies by ELISA and Western blotting, and neurological involvement was monitored by testing of cerebrospinal fluid (CSF) and PCR analysis of central nervous system (CNS) tissue obtained at necropsy. Two control nonhuman primates (NHPs), given saline injections instead of vaccine and then challenged with B. burgdorferi, developed CSF pleocytosis, PCR positivity of the brain, and high levels of specific anti-B. burgdorferi antibody in the serum and CSF. Necropsy studies revealed widespread invasion of the CNS of one of these animals by the spirochete. In contrast, none of the four vaccinated animals developed evidence of invasion of the CNS after either of two challenge inoculations with infectious B. burgdorferi. In addition to resisting infection, no vaccinated animal demonstrated any untoward consequence of vaccination. These data demonstrate that a multiantigenic vaccine is effective in preventing systemic infection and lyme neuroboreliosis in NHPs and suggest that a successful vaccine could be developed in humans which would prevent lyme disease.
Pachner
A R
AR
Georgetown University School of Medicine, Washington, DC, USA.
Delaney
E
E
Zhang
W F
WF
O'Neill
T
T
Major
E
E
Frey
A B
AB
Davidson
E
E
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000008:administration & dosage; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology*; D001483:Base Sequence; D015748:Borrelia burgdorferi Group / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D017931:DNA Primers / Q000235:genetics; D004269:DNA, Bacterial / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008193:Lyme Disease / Q000276:immunology / Q000517:prevention & control*; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D017931:DNA Primers; D004269:DNA, Bacterial