Bb architecture - antigenic variation

[Guest guest]

Cullen, Haake, and Adler disagree with Radolf and on the degree

of paucity of exposed proteins in Tp and Bb. Their 30-pp 2004 paper

in FEMS Microbiol Rev is a pretty cool treatment of spirochetal

architecture, with applications to persistence and pathogenesis.

Given that most molecular investigators seem to feel antibody to be

the key to antispirochetal immunity, it is surprising no one of this

set seems to take heed of work like Hulinskas, which visualized Bb

in seronegative patients in appreciable quantities. Since some of

these types eg Radolf (but not Barbour) vaguely seem to be aware of

the probable existence of abx-refractory chronic lyme borreliosis,

you would think they would seize upon this deficiency of specific

antibody as indicating a perhaps-fixable immune lesion possibly

necessary to the persistence of the disease.

I learned that OspC, etc, are highly polymorphic between strains.

OspA is one of the only Osps that has been found to be fairly

invariant. The invariance appears to be due to this Osp being little-

expressed in vertebrate hosts. The vertebrate adaptive immune system

can produce life-long immunity against a given microbial antigen,

which ecologically selects for the great polymorphism of the Bb

Osps. Since OspA is essentially only expressed in the tick, a much

more primitive host, it is not subject to these pressures and

remains the same in all strains. This is why it was used for the

LYMERix vaccine. Vaccination of mice with most Osps and other

exposed proteins yields immunity only to the strain from which the

vaccine is derived.

Given that most Osps cannot instill multiple-strain immunity, its

puzzling that serology works at all in lyme disease. If Ab against

one OspC fails to protect against an organism bearing a different

OspC, then how can all antibodies against various OspCs bind to the

OspC used in a western blot? Hmmm. Perhaps the WB employs not only

Osp epitopes that are surface-exposed, but also others that are not,

and that therefore are not very polymorphic and not very important

in immunity to Bb. I guess that is the most likely answer.

These authors propose that antigenic variation could well be a major

cause of Bb persistence.