New Study Shows First Candidate Quadrivalent Conjugate Meningococcal Vaccine is Safe and Immunogenic in Adolescents

CHICAGO -- Study findings, presented today at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), show Aventis' candidate multi-serogroup conjugate vaccine for meningococcal disease was well-tolerated and immunogenic in a population of healthy 11- to 18-year-olds.

"These new study results are very encouraging for the prevention of multiple serogroups of meningococcal disease in the U.S. because conjugate vaccines typically induce an immune response that is associated with long-term disease protection," said Harry Keyserling, MD, professor of pediatrics at Emory University in Atlanta, principal investigator for the study. Keyserling presented the findings at the scientific meeting.

Five serogroups of meningococcal disease (known as A, B, C, Y, and W-135) are responsible for nearly all cases of meningococcal disease in the world. No vaccine exists for serogroup B; the data show that the candidate conjugate vaccine, MCV-4, is immunogenic against the remaining four serogroups (A, C, Y, and W-135). MCV-4 is being developed by Aventis Pasteur, the vaccines business unit of Aventis, which also supplies Menomune(R)-A/C/Y/W-135 (Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined), a polysaccharide meningococcal vaccine now on the market.

Meningococcal disease is a rare but devastating bacterial infection and the leading cause of bacterial meningitis, which strikes between 2,500 and 3,000 Americans -- mostly children and adolescents -- every year, killing 300 or more and leaving others with permanent disabilities such as hearing loss, brain damage, and limb amputations.

The disease is most common in children under age 4. During the 1990s, incidence increased substantially among 15- to 24- year-olds, and one study found a 22.5 percent fatality rate among people in this age group who contracted meningococcal disease.

Different types of vaccines induce different levels of immune response. Menomune vaccine is made from long-chain polysaccharides that come from the outer coat of the meningococcus bacterium. Vaccines made using this technology may provide a limited duration of immunity. In the case of Menomune vaccine, protection against meningococcal disease lasts for 3 to 5 years. Immature immune systems of very young children respond poorly to polysaccharide vaccines.

MCV-4 is a conjugate vaccine, made by attaching the meningococcal polysaccharides to a carrier protein. Historically, conjugate vaccines have been shown to induce boostable memory responses and longer-lasting immune responses than polysaccharide vaccines. Since 1990, vaccines employing conjugate technology have substantially reduced two other bacterial infections that were major causes of bacterial meningitis in young children: Haemophilus influenzae type b and Streptococcus pneumoniae.

Experience in the United Kingdom (U.K.) may provide a model for the potential impact of MCV-4 in the U.S. From 1999 to 2000, the U.K. ran a national campaign to immunize 15 million children under age 17 with a conjugate vaccine that offered protection against one serogroup (the C serogroup) of meningococcal bacteria. The campaign resulted in an 85 percent overall decline in cases and 90 percent reduction in deaths from meningococcal disease one year later.

Disease rates declined among unvaccinated children as well as among those who were vaccinated, suggesting that the vaccine suppressed transmission of the infection in the unvaccinated population, thus offering the public health benefits of herd immunity.

Obtaining the same public health benefits in the U.S. would require a vaccine that protects against multiple serogroups of meningococcal bacteria. Four serogroups of the bacteria (C, Y, W-135, and B) predominate in the U.S. MCV-4 contains three of these four serogroups, which cause approximately two-thirds of meningococcal disease overall and 79 percent percent in the adolescent population. In the U.K., by contrast, two serogroups (C and B) predominate; the C serogroup alone caused 38 percent of meningococcal disease in that country prior to vaccination. There is no vaccine against meningococcal disease caused by the B serogroup.

"The new findings presented here today about Aventis Pasteur's candidate multi-serogroup conjugate vaccine MCV-4.taken together with the U.K.'s experience with a conjugate meningococcal vaccine.offer reason for optimism that substantial control of bacterial meningitis in the United States is within our grasp," said Michael Decker, MD, vice president of scientific and medical affairs at Aventis Pasteur Inc.

Source: Aventis Pasteur