Immunotherapy for Infectious Diseases

Bacterial Infections and Sepsis 277
Other Gram-Positive Organisms
The use of specific hyperimmune globulins in the treatment of diseases associated
with toxins produced by corynebacteria and clostridia is now well established (13–15).
Diphtheria antitoxin, when administered early in the disease, appears to prevent a number
of complications associated with diphtheria (13). Similarly, the use of tetanus and
botulinum antitoxins is critical to the recovery of patients with tetanus and botulism
(14,15). One anecdotal study suggested that the use of IVIG facilitated the resolution
of Clostridium difficile enterocolitis (16).
Gram-Negative Cocci and Coccobacilli
Hemophilus influenzae is an important cause of invasive disease, especially meningitis,
in infants and young children. An effective vaccine directed against a major outer
membrane protein, as well as a vaccine directed against the specific polysaccharide,
has now been in routine use (17). Currently available antibiotics are still very effective
against disease caused by H. influenzae in children and adults; thus, it would not appear
necessary to try to develop hyperimmune antisera for adjunctive use in the treatment
of serious infections caused by this organism.
Neisserial infections, especially those caused by Neisseria meningitidis and Neisseria
gonorrhea, remain worldwide problems. Vaccines have been developed for Groups
A and C meningococci, and work is proceeding on developing a vaccine for group B
as well (18,19). Work is also proceeding on the development of a gonococcal-specific
vaccine (20). As for the potential use of hyperimmune IVIG preparations directed
against meningococci or gonococci, there would not seem to be any compelling need
for the development of such sera.
Gram-Negative Bacilli
Much attention has been paid to the prevention and treatment of infections caused
by enteric Gram-negative bacilli and Pseudomonas aeruginosa. Infections caused by
these organisms have been of increasing importance as pathogens, especially in hospitals,
causing significant morbidity and mortality (21). As more immunosuppressive
treatments are used to control malignancies and other disorders, the incidence of secondary
infections caused by Gram-negative bacilli increases. The ability of these
organisms to become resistant to antibiotics over relatively short periods also presents
a compelling argument for the development of effective prophylactic and therapeutic
strategies to combat the frequently life-threatening infections associated with them. It
would appear at times that significant progress has been made in this area, only to find
evidence to the contrary. Nonetheless, the bulk of the evidence supports the idea that
successful immunization against these organisms is possible and that immunotherapy
of infection in progress is also possible.
Braude et al. (22) and McCabe (23) made the initial observations that the core glycolipids
of the endotoxin molecule, common to all Enterobacteriaceae, could be used
to prevent infection from both homologous and heterologous enteric bacteria and that
antisera directed against this endotoxin core could both prevent and treat infections
caused by different enteric bacteria. Clinical trials initially using human antiserum to
the core of the endotoxin molecule of a mutant E. coli, and subsequently a monoclonal