The outer surface protein A (OspA) vaccine against Lyme disease: 
efficacy in the rhesus monkey

Vaccine 1997 Volume 15 Number 17/18, pages 1872-1887.

Mario T. Philipp*¦¦, Yves Lobet†, Rudolf P. Bohm Jr.*, E. Donald 
Roberts*, Vida A. Dennis*, Yan Gu*, Robert C. Lowrie Jr.*, Pierre 
Desmons†, Paul H. Duray‡, John D. England§, Pierre Hauser†, Joseph 
Piesman¶ and Keyu Xu*

*Tulane University Medical Center, Tulane Regional Primate Research 
Center, Covington, LA, USA. †SmithKline Beecham Biologicals, Rixensart, 
Belgium. ‡National Cancer Institute, National Institutes of Health, 
Bethesda, MD, USA. §Department of Neurology, Louisiana State University, 
New Orleans, LA, USA. ¶Division of Vector-Borne Infectious Diseases, 
Centers for Disease Control and Prevention, Fort Collins, CO, USA. ¦¦To 
whom correspondence should be addressed.  Tel.: (504) 892-2040; fax: 
(504) 893-1352;  e-mail:  philipp@tpc.tulane.edu.  (Received 19 February 
1997;  revised version received 12 April 1997; accepted 6 May 1997)

The efficacy of an outer surface protein A (OspA) vaccine in three 
different formulations was investigated in the rhesus monkey.  The 
challenge infection was administered using Ixodes scapularis ticks that 
were infected with the B31 strain of Borrelia burgdorferi.  Protection 
was assessed against both infection and disease, by a variety of 
procedures.  Some of the animals were radically immune suppressed, as an 
attempt to reveal any putative low level infection in the vaccinated 
animals.  The significant difference found between the spirochaetal 
infection rates of ticks that had fed on vaccinated vs. control monkeys, 
lack of seroconversion in the vaccinated animals, and the absence of 
spirochaetal DNA in the skin of vaccinated animals in the weeks 
following the challenge, indicate that vaccinated monkeys were protected 
against tick challenge.  The post-mortem immunohistochemical and 
polymerase chain reaction analyses, however, suggest that these monkeys 
may have undergone a low-level infection that was transient.  1997 
Elsevier Science Ltd. 

Keywords: vaccine efficacy; OspA; Borrelia burgdorferi; Lyme disease

Recombinant outer surface protein A (OspA) is currently the most 
developed, molecularly-defined vaccine candidate to prevent Lyme 
borreliosis.  This disease, which is caused by the spirochaete Borrelia 
burgdorferi and is transmitted to humans by ticks, continues to be the 
most frequently-reported arthropod-borne malady in the United States and 
Europe (1,2).  An infection with B. burgdorferi may affect multiple 
organs, including the dermal, musculoskeletal, ocular, reticulo-
endothelial, cardiac or nervous systems, and although timely 
administration of appropriate antibiotics is usually curative, long 
courses of therapy may be required if the infection is allowed to become 
chronic, and in some patients there is no response to therapy at all 
(3).  This occasional refractoriness to treatment substantiates the need 
for immunoprophylactic strategies.
   The safety and immunogenicity of recombinant OspA vaccines have been 
evaluated in both naive and B. burgdorferi-infected rhesus monkeys (4), 
as well as in human subjects without (5,6) and with (7) a previous 
history of Lyme disease but with no evidence of active infection.  These 
evaluations have consistently indicated that OspA-based vaccines are 
safe.  Proof of the 'principle' that OspA is a protective antigen was 
achieved with both passive and active immunisation experiments in 
rodents (8,9) (see reference (10) for a review).  More recently, vaccine 
formulations that are compatible with human use were also shown to be 
efficacious in mice (11,13).  In addition, phase III human trails are 
underway (14).
   The present study of efficacy of OspA vaccines in the rhesus monkey 
was undertaken to ascertain if different vaccine formulations, including 
one currently used in the phase III human trials, were able, at the very 
least, to induce protection against disease and, at best, to elicit 
sterile immunity in the rhesus monkey. The animal model was chosen 
because it was shown previously that rhesus monkeys infected with B. 
burgdorferi develop disease signs that mimic both the acute and chronic 
phases of Lyme disease in humans.  These signs include erythema migrans, 
arthritis, myocarditis and neuroborreliosis (15-19).  At the serological 
level, too, the time course and specificity spectrum of the antibody 
response to B. burgdorferi in rhesus monkeys have been shown to be 
similar to their counterparts in humans (15).  Thus, by choosing the 
rhesus monkey for this study we sought to retain the case with which 
evidence of infection may be gathered in an animal model, without 
relinquishing the possibility of assessing protection against disease 
manifestations that most closely resemble human Lyme disease.

-----
See complete document at:
The outer surface protein A (OspA) vaccine against Lyme disease: 
efficacy in the rhesus monkey 
[Vaccine 1997 Volume 15 Number 17/18, pages 1872-1887]
http://www.geocities.com/HotSprings/Oasis/6455/rhesus-index.html