03/19/2012 12:07 EDT | Updated 05/19/2012 05:12 EDT

Use of pneumococcal vaccine in children driving strains out of adults too

TORONTO - Can a vaccine work too well?

For an individual, probably not. But for the makers of newer pneumococcal vaccines that were first marketed for kids but which are now being aimed at older adults, it may turn out that the answer is actually yes.

There has been a large spillover effect in adults from the use of these vaccines in children, studies show. So large, in fact, that adults appear to be getting the benefits of the vaccines without having been vaccinated — a bonus that may actually undermine the efforts of one manufacturer, Pfizer, to promote widespread use of its pneumococcal vaccine in older adults.

"It may have worked too well in children to make it necessary in adults. It's quite possible," admits Dr. Jeffrey Duchin, head of the communicable disease epidemiology and immunization section of Seattle and King County Public Health Department and a professor in the school of public health at the University of Washington.

"The childhood vaccination program may have such positive indirect effects on adult invasive pneumococcal disease that the rationale for vaccinating adults is much less strong."

This is a story of herd immunity in action.

That term describes the phenomenon of protecting a group of people — the herd — by protecting enough individual members so that a pathogen cannot continue to spread efficiently within the group. It takes different rates of vaccination to achieve herd immunity for individual bacteria or viruses, depending on factors like how contagious the pathogen is, how many strains of it exist and whether infection with or vaccinating against one strain offers protection against others.

In this case, the disease agent is Streptococcus pneumoniae bacteria, a major cause of pneumonia in adults and children, and of inner ear infections in young kids. As well, the bacteria can invade the blood, the cerebrospinal fluid, or more rarely the fluid in joints, or the lining of the lungs or heart — a development called invasive pneumococcal disease.

The newer vaccines were brought to market to protect against invasive pneumococcal disease, which can trigger meningitis and blood infections, sometimes with tragic consequences. These severe infections can cause permanent hearing loss or brain damage, and some children who suffered from acute blood infections have lost fingers and toes.

In 2002, the National Advisory Committee on Immunization estimated that annually in Canada invasive disease in children younger than five caused 65 cases of meningitis, 700 cases of bacteremia (blood infection) and 9,000 cases of pneumonia that didn't require hospitalization. In children, those under five and especially those under two years of age have the highest risk of developing serious pneumococcal disease.

There's been a pneumococcal vaccine for seniors available for years. It's a 23-valent vaccine, meaning it protects against 23 strains or serotypes of Streptococcus pneumoniae, targeting sugars in the bacteria. (There are more than 90 serotypes of the bacteria, but vaccine production has focused on the ones that caused the most and the worst disease.)

But this type of vaccine doesn't work with the developing immune systems of children. So kids were unprotected until 2000, when drug giant Pfizer brought to market the first of the so-called pneumococcal conjugate vaccines, which do work in kids. The first vaccine, marketed under the name of Prevnar 7 because it protected against seven serotypes of the bacteria, was introduced to the Canadian market in 2001, though it was a few years before it was added to the schedule of publicly funded vaccines.

Even from the earliest days of its use the vaccine started to drive down the numbers of invasive disease caused by the seven vaccine serotypes, says Dr. Allison McGeer, an infectious diseases specialist at Toronto's Mount Sinai Hospital.

Before the vaccine was available, Toronto would record 30 cases of invasive pneumococcal disease per 100,000 children each year. But by 2004, it had tumbled to 15 cases a year — even though the expensive vaccine wasn't yet being paid for by the Ontario government and only about a quarter of eligible children were getting it. Once the vaccine was added to the public program in 2005, the number of cases of invasive pneumococcal disease dropped to five per 100,000 children.

Pfizer has since replaced Prevnar 7 with Prevnar 13, which broadens the protection. It was approved in the United States and Canada in 2009 and rolled out the following year. It is now offered free in all provinces and territories.

Though it was slower to get its version to market, GlaxoSmithKline now has a pneumococcal conjugate vaccine called Synflorix which protects against 10 serotypes. It received approval for use in children in Canada in early January. It hasn't yet been tested in seniors, so GSK isn't currently trying to get approval to market it to that demographic.

Pfizer would now like to market Prevnar 13 to older adults and seniors, and in mid-February the company announced Health Canada had approved the vaccine for use in adults 50 and older. In the U.S., the company has asked the Advisory Committee on Immunization Practices (ACIP) to recommend use of Prevnar 13 in older adults. An ACIP recommendation generally results in a vaccine being added to the list of those covered by American health insurance companies.

"There are financial implications (of a recommendation) for both the patient and the manufacturers and the payers. And there's a big boost in sales because once ACIP recommends a vaccine ... most health-care providers will comply with that," says Duchin, who is currently a member of ACIP.

But a presentation to that committee last month underscores a problem Pfizer faces in making major inroads into the older adult market. A working group set up by the advisory committee to study whether the vaccine should be recommended for older adults is advocating a wait-and-see approach.

Duchin, who is also on the working group, says that is in part due to the fact that when Prevnar 7 started to be used in children, public health researchers noticed a sharp drop in seniors of cases of invasive pneumococcal disease caused by the seven vaccine strains.

"It's been very dramatic in the United States and it's certainly been suggestive in a number of other places," says Marc Lipsitch, an infectious diseases epidemiologist who teaches in Harvard University's School of Public Health.

Public health experts are waiting to see whether the dramatic herd effect that resulted from Prevnar 7 will be repeated with Prevnar 13.

"We are seeing early evidence of declines in disease caused by two of the new antigens in PCV13 among children, but it’s a little too early to tell for sure among adults," says Dr. Cynthia Whitney, an pneumococcal expert at the U.S. Centers for Disease Control. (Most people in public health refer to the pneumococcal conjugate vaccines by the generic names PCV7, PCV10 and PCV13.)

Duchin says another year or two of use should start to tell the tale. But if using the vaccine in children drives those 13 serotypes out of circulation or even down to ultra low levels, there might be little to be gained by suggesting adults get Prevnar 13, especially given that the older and cheaper 23-valent pneumococcal vaccine is already an option for them.

The company is arguing that there should be another advantage of using the vaccine in seniors, saying it would also protect older adults against pneumonia caused by Streptococcus pneumoniae. Pneumonia can be caused by a variety of pathogens but Streptococcus pneumoniae accounts for about 30 to 40 per cent of cases, McGeer says.

There isn't a lot of evidence at this point to suggest whether Prevnar 13 is better at protecting against pneumococcal pneumonia than the 23-strain vaccine, though a study is currently underway in the Netherlands trying to answer that question. The results plus the observations on herd immunity with the 13 Prevnar serotypes should decide this vaccine's future as a tool to protect seniors, experts say.

"When those data become available, we'll be able to make a much better decision about whether it makes sense to use the vaccine or not. But right now, there are not a lot of data that would push you to substitute this vaccine for the 23-valent (vaccine)," Duchin says.