An experimental vaccine designed to protect against group A streptococcal infection, which can cause strep throat and more serious diseases such as scarlet fever, is safe and well tolerated, researchers report.

Moreover, the vaccine is capable of triggering vigorous bacteria-killing immune responses, according to results of an early trial in volunteers, reported in this week’s Journal of the American Medical Association.

However, safety concerns regarding potential cross-reaction with human tissues mean that years of study remain before a group A streptococcal (GAS) vaccine can be approved for public use, an expert asserts in an accompanying editorial.

“It has been about 30 years since a streptococcal vaccine even went into clinical trial,” lead researcher Dr. Karen L. Kotloff told Reuters Health.

All GAS vaccines have been based on the M protein found on the surface of the bug, but antibodies produced against this antigen can also target human tissues - which is why rheumatic heart disease can be a long-term consequences of group A strep infection.

In fact, this “cross-reactivity” between M protein and human tissue did lead to increased rates of rheumatic fever among people given the earlier vaccines, bringing clinical testing to a halt.

“What enabled this trial to go forward is that very detailed studies of M protein made it possible to tease out areas of the protein thought to be involved in stimulating protective immunity from those involved in stimulating an autoimmune response,” Kotloff explained. “The ability to separate these areas gave scientists the confidence that we could again begin clinical testing of a GAS vaccine.”

Kotloff, at the University of Maryland School of Medicine in Baltimore, and associates constructed a synthetic peptide for use as a GAS vaccine, containing fragments of M protein from six strains of the bacteria that cause strep throat and rheumatic fever.

They tested the vaccine in 28 healthy adult volunteers ages 18 to 50. Each volunteer was given three spaced injections of the vaccine into the deltoid muscle of alternating arms, then underwent one year of intensive follow-up.

Vaccination was well tolerated with local reactions graded as mild or moderate. There were no cases of unexplained or persistent fever, or of late effects associated with GAS infection, the authors note, and no evidence of tissue cross-reactive antibodies.

The highest vaccine dose prompted increases in functioning antibody levels against all six component M antigens. The team also showed that blood from the vaccinated participants killed group A strep in a lab dish.

“At this preliminary stage this was very promising news, suggesting that additional development of this concept is warranted,” Kotloff continued.

She added, “As a next step, a vaccine was made including 26 types of GAS believed to include 80 to 90 percent of the important types in this country. That vaccine is now in clinical trial in Canada.”

In his editorial, Dr. Michael Pichichero, at the University of Rochester Medical Center in New York, comments that “the regulatory challenges for GAS vaccines are substantial.” The need to rule out rare adverse events will require trials involving up to 60,000 subjects before it can be licensed.

Nevertheless, he maintains, the report by Kotloff’s group “is a positive step in a long journey ahead to develop a GAS vaccine.”

SOURCE: Journal of the American Medical Association, August 11, 2004.