Immunotherapy for Infectious Diseases

276 Donta
no controlled clinical trials have been conducted to evaluate its potential fully, and no
TSST-specific, hyperimmune, sera have been developed to further evaluate their potential
efficacy in reducing the morbidity and mortality of this disease.
Because staphylococci, especially S. aureus, have become increasingly resistant to
antibiotics currently in use, emphasis should be placed on the development of both
active vaccines and hyperimmune sera directed against specific antigens to prevent and
treat invasive disease.
Streptococci
Prior to the advent of antimicrobials, antisera were developed to combat pneumococcal
infections, especially pneumonia (7). The use of these preparations became standard
practice and did lead to a significant reduction in the mortality of the disease. As
effective antibiotics were developed, the use of antipneumococcal sera was abandoned.
Now that strains of pneumococci have become resistant to �-lactams, it may become
necessary to reconsider the use of antisera as adjunctive, if not primary, therapy of serious
pneumococcal infections. It should not be difficult to prepare hyperimmune sera
from individuals immunized with polyvalent preparations of pneumococcal polysaccharides
who have high titers against the prevalent serotypes of pneumococci.
No antisera directed against the polysaccharides or proteins of any of the hemolytic
streptococci have been developed to date. In studies of the use of various intravenous
immunoglobulin (IVIG) preparations in the prevention and treatment of sepsis in lowbirth-weight
and other neonates, there appeared to be a small, but significant effect on
decreasing the mortality rate associated with sepsis (8,9). Group B streptococci are an
important cause of neonatal sepsis, but these studies did not specifically address these
organisms, and it is as yet unclear whether the use of standard IVIG preparations would
prevent or augment the treatment of serious group B streptococcal infections. Group B
streptococci can also cause serious disease in adults, especially those with underlying
diabetes, cirrhosis, and malignancy, but these infections have not posed a threat in
terms of antibiotic resistance, and it would seem unlikely that hyperimmune antisera
to group B streptococcal antigens would significantly facilitate the resolution of the
disease, compared with the use of antibiotics alone. It would seem important, however,
to develop vaccines against specific group B streptococcal antigens for use in susceptible
adults, if not in neonates.
Group A streptococcal infections remain an important cause of morbidity and mortality
in most human populations. Attempts to develop vaccines that induce protective
immunity have faltered because of potential cross-reactions with normal human tissues
(10). Nonetheless, these attempts should continue, as should the development of specific,
hyperimmune sera, to augment the treatment of serious infections such as necrotizing
fasciitis, septicemia, and complicated cellulitis. Streptococcal toxins, especially
TSST, appear to be important virulence factors in the pathogenesis of systemic infection
(11), and the early use of IVIG, similar to that in staphylococcal infections,
appears to ameliorate the effects of TSST-associated streptococcal infections (12). Ideally,
controlled clinical studies should be conducted to prove that this approach would
work. In this regard, hyperimmune sera directed against TSST should be developed for
use in such studies, and for use in selected clinical situations.