Safety and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine after one or two doses given to infants and toddlers.

With the emergence of multiple meningococcal serogroups in different geographic areas, broad vaccine protection from infancy is desirable. One hundred and seventy-five infants received either two doses of a meningococcal quadrivalent (A, C, W-135, Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM at 18 months. Bactericidal antibody titers using human complement were measured before and 1 month after each dose. Injection-site reactions were reported by 22-45% of participants following MenACWY-CRM given at 6 or 12 months. Similar proportions of subjects had injection-site reactions following two doses of MenACWY-CRM (32-41%) or one dose of MenC (26-44%). The incidence of systemic adverse events was comparable between groups. After two doses of MenACWY-CRM, the percentages of participants reporting hSBA titers >or=8 were 100% for C, W-135, and Y, and 84% for A. Serogroup C titers were more than 10-fold higher after two doses of MenACWY-CRM than after one dose of MenC or MenACWY-CRM at 12 months. Serogroup C titers were comparable following a single dose of MenACWY-CRM or MenC at 12 months. MenACWY-CRM is well tolerated and immunogenic given at 12 months, or two doses at 6 and 12 months of age.

Preventing teenage pregnancy.

Teenage pregnancy is still a medical and economic concern. Early anticipatory counseling with an emphasis on abstinence is helpful. Contraception information and sexually transmitted disease prevention should be part of the counseling. This article reviews common contraception methodology.

PIP: The topic of preventing adolescent pregnancy in developed countries is introduced by noting that 1) adolescent pregnancy in the US, the UK, and Canada is associated with financial dependence on social services and with increased health risks for the mother and child; 2) these negative outcomes call for preventive efforts that target adolescents at risk and provide contraceptive information to adolescents at an early age; 3) poverty is the most prevalent risk factor; and 4) one screening technique, dubbed HEADS, considers home life, education, activities, drug use, sex behavior, and suicidal tendencies. After recommending that primary care givers first emphasize abstinence and then give accurate and complete information about contraceptive methods, the remainder of the article reviews the following methods: barrier methods, IUDs, oral contraceptives (OCs), Norplant, injectable progesterone, and postcoital (emergency) contraception. The text is illustrated with tables that 1) compare female barrier methods, 2) describe OC contraindications, 3) compare hormonal components in common OCs, 4) list the contraindications to Norplant, 5) show OC noncompliance rates among adolescents, 6) show barrier method noncompliance rates among adolescents, and 7) illustrate the failure rates of different contraceptive methods. The article concludes by recommending that counseling on prevention of sexually transmitted diseases should accompany contraceptive counseling and by noting that increased knowledge is not associated with increased sex behavior or decreased age of initial intercourse.

Polysaccharide-protein conjugate vaccination induces antibody production but not sustained B-cell memory in the human nasopharyngeal mucosa.

Colonization of the nasopharyngeal mucosa by meningococcus and other polysaccharide (PS)-encapsulated bacteria precedes invasion. PS-conjugate vaccines induce PS-specific B-cell memory (B(MEM)) and also prevent colonization, thus blocking person-to-person transmission, generating herd protection. However, in isolation the B(MEM) are unable to sustain immunity. Furthermore, the duration of herd protection the vaccines induce appears limited. We demonstrate that, despite the persistence of PS-specific B(MEM), the population is not maintained within the nasopharynx. Although booster immunization results in the transient appearance of PS-specific B(MEM) within the mucosa, this reflects the re-circulation of systemic B(MEM) through the site rather than the generation of resident mucosal B(MEM). The induction of sustained PS-specific B(MEM) in the nasopharynx would allow the population to be activated by colonization, thus inhibiting subsequent invasion. It would also be expected to boost local mucosal immunity, thus extending herd protection. Strategies to generate PS-specific B(MEM) in the mucosa warrant further investigation.

Safety and immunogenicity of an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in Latin America.

BACKGROUND: This study compared the investigational quadrivalent meningococcal CRM197 conjugate vaccine, MenACWY-CRM, with licensed quadrivalent polysaccharide (MPSV4) and conjugate (MenACWY-D) meningococcal vaccines. METHODS: In this phase III multicenter study, 2505 adults (aged 19-55 years) were randomized to receive either MenACWY-CRM or MenACWY-D, and 326 adults (aged 56-65 years) were randomized to receive either MenACWY-CRM or MPSV4. Sera obtained pre-vaccination and at 1-month post-vaccination were tested for serogroup-specific serum bactericidal activity using human complement (hSBA) for immunogenicity non-inferiority and superiority analyses. RESULTS: The vaccines in all groups were well tolerated. In the 19-55 years age group, post-vaccination geometric mean titers (GMTs) were consistently higher for MenACWY-CRM than for MenACWY-D for all four serogroups. MenACWY-CRM was non-inferior to MenACWY-D for all serogroups, and superior for serogroup Y. In the 56-65 years age group, post-vaccination GMTs were 1.2- to 5.4-fold higher for MenACWY-CRM than for MPSV4 for the four serogroups. CONCLUSIONS: MenACWY-CRM is well tolerated and immunogenic in adults aged 19-65 years, with at least non-inferior immunogenicity compared with the currently licensed meningococcal vaccines.

Immunogenicity and tolerability of a quadrivalent meningococcal glycoconjugate vaccine in children 2-10 years of age.

Meningococcal disease incidence is highest in infants, but a significant burden of disease also occurs in children. In this Phase II, single-centre US study, 619 healthy children (2-10 years of age) received one dose of an investigational quadrivalent meningococcal CRM(197)-conjugated vaccine (MenACWY-CRM) or a licensed quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immunogenicity was assessed using the serum bactericidal assay with human complement (hSBA) at 1 and 12 months post-vaccination. Local and systemic reactions were recorded for 7 days, all adverse events (AEs) for 1 month, and medically significant and serious AEs (SAEs) for 12 months post-vaccination. For all four serogroups, more MenACWY-CRM recipients achieved an hSBA titre >or=1:4 at 1 month post-vaccination (A: 82%; C: 83%; W-135: 95%; Y: 91%) compared with the group that received MPSV4 (A: 45%; C: 66%; W-135: 71%; Y: 61%); this difference persisted through to 12 months post-vaccination. Both vaccines were well tolerated. In children 2-10 years of age, MenACWY-CRM induced a higher immune response than that of MPSV4, and was well tolerated.

Safety and immunogenicity of one dose of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, when administered to adolescents concomitantly or sequentially with Tdap and HPV vaccines.

This Phase III study evaluates an investigational quadrivalent meningococcal CRM(197) conjugate vaccine, MenACWY-CRM (Novartis Vaccines), when administered concomitantly or sequentially with two other recommended adolescent vaccines; combined tetanus, reduced diphtheria and acellular pertussis (Tdap), and human papillomavirus (HPV) vaccine. In this single-centre study, 1620 subjects 11-18 years of age, were randomized to three groups (1:1:1) to receive MenACWY-CRM concomitantly or sequentially with Tdap and HPV. Meningococcal serogroup-specific serum bactericidal assay using human complement (hSBA), and antibodies to Tdap antigens and HPV virus-like particles were determined before and 1 month after study vaccinations. Proportions of subjects with hSBA titres > or =1:8 for all four meningococcal serogroups (A, C, W-135, Y) were non-inferior for both concomitant and sequential administration. Immune responses to Tdap and HPV antigens were comparable when these vaccines were given alone or concomitantly with MenACWY-CRM. All vaccines were well tolerated; concomitant or sequential administration did not increase reactogenicity. MenACWY-CRM was well tolerated and immunogenic in subjects 11-18 years of age, with comparable immune responses to the four serogroups when given alone or concomitantly with Tdap or HPV antigens. This is the first demonstration that these currently recommended adolescent vaccines could be administered concomitantly without causing increased reactogenicity.