La vacunación antineumocócica en Cuba. Retos y desafíos

El desarrollo de la Medicina ha reflejado la necesidad de prevenir enfermedades trasmisibles a través de vacunas. Después de la descripción del papel que juega el neumococo en la génesis de enfermedades, se inició una carrera destinada a prevenirlas. En el presente siglo se licenció la primera vacuna conjugada contra el Streptococcus pneumoniae para ser utilizada en niños. En Cuba, a pesar de los esfuerzos realizados, no se ha introducido la vacuna antineumocócica y desde hace más de una década se trabaja en un candidato vacunal conjugado heptavalente, actualmente en evaluación clínica avanzada. En este trabajo se hacen consideraciones al respecto.

Medicine development has shown the need of preventing transmissible diseases by means of Vaccines. After a description of the role of pneumococcus in the origin of diseases, a career towards preventing them was started. In the current century, the first conjugated vaccine was certified against Streptococcus pneumonia to be used in children. In Cuba, in spite of the efforts, the anti-pneumococcal vaccine has not been introduced and for more of a decade time scientists have been working in a heptavalent conjugated vaccine, currently in an advanced clinical evaluation. In this work, considerations in this regard are made.

Impact of IgM Antibodies on Cross-Protection against Pneumococcal Serogroups 6 and 19 after Immunization with 7-Valent Pneumococcal Conjugate Vaccine in Children

Although it is well known that pneumococcal conjugate vaccines provide cross-protection against some vaccine-related serotypes, these mechanisms are still unclear. This study was performed to investigate the role of cross-protective IgM antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in children aged 12-23 months after immunization with 7-valent pneumococcal conjugate vaccine (PCV7). We obtained serum samples from 18 Korean children aged 12-23 months after a PCV7 booster immunization. The serum IgG and IgM concentrations of serotypes 6B and 19F were measured by enzyme-linked immunosorbent assay (ELISA) in serum. The opsonic indices (OIs) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were determined by an opsonophagocytic killing assay (OPA) in IgM-depleted and control serum. Both IgG and IgM antibodies in ELISA and opsonic indices in OPA against serotypes 6B and 19F were demonstrated in the immune serum. IgM depletion decreased the OIs against vaccine serotypes 6B (geometric means of OIs (GMIs) of 3,009 vs. 1,396, 38% reduction) and 19F (1,117 vs. 750, 36% reduction). In addition, IgM depletion markedly decreased the OIs against vaccine-related serotypes 6A (GMIs of 961 vs. 329, 70% reduction), 6C (432 vs. 185, 72% reduction), and 19A (301 vs. 166, 58% reduction). The booster immunization PCV7 induced protective antibodies in the form of both IgG and IgM isotypes. IgM antibodies contributed to eliciting cross-protection against vaccine-related serotypes as well as against vaccine serotypes.

Cross-reaction of 6B and 19F Specific Antibodies to Serotypes 6A, 6C, and 19A after Immunization with 7-valent Pneumococcal Conjugate Vaccine in Korean Children Aged 12-23 Months / 소아감염

PURPOSE: The cross-protection of 7-valent pneumococcal conjugate vaccine (PCV7) against vaccine-related serotypes has been controversial. We investigated the serological properties of cross-protective antibodies against vaccine-related serotypes 6A, 6C, and 19A induced in young children aged 12-23 months after booster immunization of PCV7. METHODS: IgG and IgM antibody concentrations and opsonic index (OI) against vaccine serotypes 6B and 19F and vaccine-related serotypes 6A, 6C, and 19A were measured by ELISA and opsonophagocytic killing assay (OPA) in 4 selected immunesera. The serological properties and antigenic specificity of protective antibodies were determined by IgM depletion of immunesera, OPA, and competitive OPA against serogroup 6 and 19 pneumococci. RESULTS: Compared to pre-IgM depleted immunesera, OI of IgM-depleted immunesera against 6B and 19F decreased and OI against 6A, 6C, and 19A decreased, too. In competition OPA, free 6B and 19F polysaccharide completely inhibited the immune protection against vaccine-related serotypes 6A, 6C, and 19A as well as vaccine types 6B and 19F. CONCLUSIONS: The booster immunization of PCV7 certainly induced cross-protective antibodies against vaccine-related serotypes 6A, 6C, and 19A with both IgG and IgM isotypes. Furthermore, IgM antibodies are more highly contributed to opsonophagocytic activity against vaccine-related serotypes as well as most of vaccine types than do IgG antibodies. Further studies are needed for the more immunized sera in the children as well as adults.

Nasopharyngeal Pneumococcal Carriage of Children Attending Day Care Centers in Korea: Comparison between Children Immunized with 7-valent Pneumococcal Conjugate Vaccine and Non-immunized

To confirm the effect of 7-valent pneumococcal conjugate vaccine (PCV7), pneumococcal nasopharyngeal (NP) carriage was compared between vaccinated (3 + 1 doses PCV7) and non-vaccinated children. Vaccinated subjects were recruited from highly vaccinated regions (> or = 60%), Seoul and Incheon whereas control subjects were recruited from Jeju Island where vaccination rates are low (< 15%). NP swabs were obtained from 400 children aged 18-59 months. Serotype and antibiotic susceptibility was analyzed. Pneumococcal carriage rate was 18.0% (36/200) and 31.5% (63/200) for the vaccinated and control group, respectively. Among those vaccinated, 41.7% (15/36) of the serotypes were vaccine-related type (VRT: 6A, 6C, 19A) with the most common serotype 6C. The next common type was non-typable/non-capsule 30.6% (11/36) followed by non-vaccine type 16.7% (6/36) and vaccine type (VT) serotypes were found in only 11.1% (4/36). In contrast, 52.4% (33/63) of the isolates in the control group were VT. Resistance rates for penicillin and erythromycin were lower in the vaccine group (vaccine vs control; penicillin 45.2% vs 71.4%, erythromycin 74.2% vs 90.5%, P < 0.05). Multi-drug resistance was also lower in vaccinated subjects (vaccine vs control; 45.2% vs 69.8%, P < 0.05). PCV7 reduces carriage in VT which leads to replacement of pneumococci by antibiotic susceptible VRT or non-vaccine type strains.

Immune response to 19A serotype after immunization of 19F containing pneumococcal conjugate vaccine in Korean children aged 12-23 months / 소아과

PURPOSE: The purpose of this study was to evaluate the immune response to serotype 19A in children aged 12-23 months after immunization of the 19F containing 7-valent pneumococcal conjugate vaccine (PCV7). METHODS: Blood samples from a total of 45 subjects (age 12-23 months) were included in the study. Subjects were categorized according to immunization status into three groups as follows: 18 subjects with 3 primary doses and 1 booster dose of PCV7 (booster group), 21 subjects with 3 primary doses before 12 months of age (primary group), and 6 subjects with no vaccination history of PCV7 (control group). An ELISA and opsonophagocytic killing assay (OPKA) was done to evaluate the immune responses against serotypes 19F and 19A. RESULTS: According to the ELISA, all subjects had antibody titers > or =0.35 microg/mL for serotypes 19F and 19A in the booster and primary group and 83.0% and 66.7% in the control group, respectively. According to the OPKA, subjects with opsonic activity (> or =20) against serotypes 19F and 19A were 100% and 61.1% of the subjects in the booster group and 66.7% and 19.0% in the primary group, respectively. No subjects in the control group had opsonic antibodies against both serotypes. CONCLUSION: In conclusion, in children 12-23 months age who were previously vaccinated with PCV7, a cross-reactive immune response is elicited against serotype 19A after a primary series of 3 doses in a small proportion of subjects, and this response is amplified after booster vaccination.