Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation

Muñoz, Flor M.; Englund, Janet A.; Cheesman, Coni C.; Maccato, Maurizio; Pinell, Phillip; Nahm, Moon H.; Mason, Edward O.; Kozinetz, Claudia A.; Thompson, Rachel; Glezen, W. Paul

doi:10.1016/s0264-410x(01)00397-8

Cited by 104 publications

(66 citation statements)

References 28 publications

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“…Significant reduction in both incidence (P ϭ 0.05) and severity (P Ͻ 0.01) of experimental pneumococcal otitis media was demonstrated in the chinchilla pups, and maternal immunization was 82% effective at preventing mortality from invasive pneumococcal disease (23). Clinical trials showed maternal immunization with PPS vaccines in the third trimester of pregnancy to be safe, and transfer of vaccine-specific antibodies was demonstrated, both in developing and industrialized countries (34,35,44,45,49,57; S. K. Obaro, Letter, Lancet 347: [192][193]1996). A trial of maternal immunization with 9-valent pneumococcal vaccines is currently being conducted in Minneapolis, Minn., to study the effect on otitis media.…”

Section: Discussionmentioning

confidence: 99%

Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria

et al. 2004

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The immune system of the newborn is immature, and therefore it is difficult to induce protective immunity by vaccination in the neonatal period. Immunization of mothers during pregnancy against infections caused by encapsulated bacteria could thus be particularly attractive, as infants do not respond to polysaccharide (PS) antigens. Transmission of maternal vaccine-specific antibodies and protection of offspring against pneumococcal bacteremia and/or lung infection were studied in a neonatal murine model of pneumococcal immunization and infections. Adult female mice were immunized with native pneumococcal PS (PPS) of serotypes 1, 6B, and 19F or PPS conjugated to tetanus protein (Pnc-TT), and PPS-specific antibodies were measured in sera of mothers and their offspring. Effective transmission of maternal antibodies was observed, as PPS-specific immunoglobulin G levels in 3-week-old offspring of immunized mothers were 37 to 322% of maternal titers, and a significant correlation between maternal and offspring antibody levels was observed. The PPS-specific antibodies persisted for several weeks but slowly decreased over time. Offspring of Pnc-TT-immunized mothers were protected against pneumococcal infections with homologous serotypes, whereas PPS immunization of mothers did not protect their offspring, in agreement with the low titer of maternal PPS specific antibodies. When adult female mice were immunized with a meningococcal serogroup C conjugate vaccine (MenC-CRM), antibody response and transmission were similar to those observed for pneumococcal antibodies. Importantly, bactericidal activity was demonstrated in offspring of MenC-CRM-immunized mothers. These results demonstrate that this murine model of pneumococcal immunization and infections is suitable to study maternal immunization strategies for protection of offspring against encapsulated bacteria.

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Section: Discussionmentioning

confidence: 99%

Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria

et al. 2004

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“…Since about one-fourth of the cases occurred in the first 3 months of life and about one-half occurred in the first 6 months, maternal immunization may be a promising strategy until a conjugate vaccine with a good immune response in early infancy is available. However, studies of maternal immunization are still preliminary, and vaccine efficacy beyond 8 weeks of age is yet to be demonstrated (23).…”

Section: Discussionmentioning

confidence: 99%

“…Alternatively, given the early age of both colonization and invasive disease, the option of maternal immunization should be considered, at least until a vaccine effective in early infancy is identified. However, transplacental antibody persists for only about 8 weeks, when pneumococcal disease prevalence is low (23,34).…”

Section: Discussionmentioning

confidence: 99%

Comparison of Antibiotic Resistance and Serotype Composition of Carriage and Invasive Pneumococci among Bangladeshi Children: Implications for Treatment Policy and Vaccine Formulation

et al. 2003

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The nasopharyngeal carriage of Streptococcus pneumoniae is thought to pose a risk for invasive pneumococcal diseases, and the evaluation of carriage strains is thus often used to inform antibiotic treatment and vaccination strategies for these diseases. In this study, the age-specific prevalences, resistance to antibiotics, and serotype distributions of 1,340 carriage strains were analyzed and compared to 71 pneumococcal strains isolated from the cerebrospinal fluid of children under 5 years old with meningitis. Overall, the nasal carriage rate was 47%. One-fourth (26%) of the infants under 1 month of age and one-half (48%) of the infants under 12 months of age were colonized with S. pneumoniae. Rural children were colonized earlier than those from urban areas. Approximately one-fourth and one-half of the cases of pneumococcal meningitis occurred in the first 3 and 6 months of life, respectively. The respective rates of resistance for carriage and meningitis strains to penicillin (7 and 3%), cotrimoxazole (77 and 69%), and erythromycin (2 and 1%) were similar, whereas chloramphenicol resistance was lower among carriage strains (3%) than among meningitis strains (15.5%). The predominant serogroups of carriage and invasive isolates were variable and widely divergent. Thus, hypothetical 7-, 9-, and 11-valent vaccines, based on the predominant carriage strains of the present study, would cover only 23, 26, and 30%, respectively, of the serotypes causing meningitis. Further, currently available 7-, 9-, and 11-valent vaccines would protect against only 26, 43, and 48%, respectively, of these meningitis cases. In conclusion, while the surveillance of carriage strains for resistance to antibiotics appears useful in the design of empirical treatment guidelines for invasive pneumococcal disease, data on the serotypes of carriage strains have limited value in vaccine formulation strategies, particularly for meningitis cases.Streptococcus pneumoniae is one of the leading causes of childhood pneumonia and meningitis. It accounts for 20 to 40% of the estimated annual global burden of 2.7 million childhood deaths from pneumonia in developing countries (11,22,25) and is the most common cause of pneumonia and the second leading cause of meningitis in children in Bangladesh (26, 31).Data on the serotype composition and antibiotic resistance of invasive pneumococcal strains from the developing world are scarce. Previously, it has been shown that the serotype distribution of invasive S. pneumoniae in Bangladesh differs from the distribution in many other parts of the world, and the proposed conjugate vaccines developed on the basis of data from other, primarily Western, countries cover at most 50% of the invasive strains (29). High levels of resistance to cotrimoxazole and low levels of resistance to penicillin have also been found (28, 30); for Bangladesh, these findings bring into question the present World Health Organization recommendation that cotrimoxazole be used as a first-line empirical therapy for the treatment of pneumon...

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“…(reviewed in reference 39). In clinical trials on maternal immunization with PPS vaccines in the third trimester of pregnancy, safety and effective transfer of vaccine-specific antibodies have been demonstrated in both developing and industrialized countries (33,40,43,46,49,57). In a trial of maternal immunization with 9-valent pneumococcal conjugate vaccine, the protective effect against otitis media as well as possible interference of MatAbs with infant responses to a 7-valent pneumococcal conjugate vaccine are being studied (13).…”

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confidence: 99%

Protective Levels of Polysaccharide-Specific Maternal Antibodies May Enhance the Immune Response Elicited by Pneumococcal Conjugates in Neonatal and Infant Mice

et al. 2005

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Maternal antibodies (MatAbs) may protect the offspring against infections but may also interfere with their immune responses to vaccination. We have previously shown that maternal immunization with pneumococcal polysaccharides (PPS) conjugated to tetanus protein (Pnc-TT) protected the offspring against infections caused by three important pediatric serotypes. To study the influence of MatAb on the immune response to Pnc-TT early in life, adult female mice were immunized twice with Pnc-TT of serotype 1 (Pnc1-TT), and their offspring received Pnc1-TT subcutaneously three times at 3-week intervals starting at 1 week (neonatal) or 3 weeks (infant) of age. High levels of PPS-1-specific MatAb (>3 log) in offspring of Pnc1-TT-immunized dams completely inhibited their anti-PPS-1 response elicited by Pnc1-TT. In contrast, low or moderate (ϳ1 to 2 log) levels of MatAb did not interfere with and even enhanced the immune response of the offspring, and a booster response to a second Pnc1-TT dose was observed. Carrier-specific MatAbs had little effect on the response of offspring to the conjugate. All Pnc1-TT-immunized offspring were protected against pneumococcal bacteremia and had reduced lung infection. These results demonstrate that in the presence of MatAb, Pnc1-TT may elicit a protective PPS-1-specific antibody response and prime for PPS-1-specific memory in young offspring. Importantly, low or moderate levels of PPS-1-specific MatAb not only provided protection against pneumococcal infections but also enhanced the immune response elicited by Pnc1-TT in neonatal and infant mice. This murine model will be used to develop novel strategies combining maternal and neonatal immunization to protect against infections caused by encapsulated bacteria in early life.

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Maternal immunization with pneumococcal polysaccharide vaccine in the third trimester of gestation

Cited by 104 publications

References 28 publications

Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria

Immunization of Female Mice with Glycoconjugates Protects Their Offspring against Encapsulated Bacteria

Comparison of Antibiotic Resistance and Serotype Composition of Carriage and Invasive Pneumococci among Bangladeshi Children: Implications for Treatment Policy and Vaccine Formulation

Protective Levels of Polysaccharide-Specific Maternal Antibodies May Enhance the Immune Response Elicited by Pneumococcal Conjugates in Neonatal and Infant Mice

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