Maternal Pneumococcal Conjugate Immunization Protects Infant Chinchillas in the Pneumococcal Otitis Media Model

Infant immunization with pneumococcal polysaccharide-protein conjugate vaccines (PCVs) is unlikely to elicit protective serum antibody concentrations during the first 4-6 months of life, when recurrent pneumococcal otitis media (POM) often begins. We therefore investigated a maternal pneumococcal immunization strategy to prevent early infant POM. Pregnant chinchillas (dams) received injections of heptavalent PCV or saline. Post-partum maternal and infant (kits) blood samples were obtained, and kits were subsequently challenged by intranasal inoculation of a vaccine-type pneumococcal strain (19F). Anti-pneumococcal capsular polysaccharide IgG antibody (Ab) concentration was measured using an ELISA in maternal and kit serum samples. Immunized dams and their kits had significantly higher Ab titers than control dams and their kits. Antibody titer in kits declined with a half-life of 12 days. Maternal immunization significantly reduced both the incidence ( p = 0.05) and severity ( p < 0.01) of experimental POM in chinchilla kits, and was 82% effective at preventing mortality from invasive pneumococcal disease. Pre-challenge serum Ab concentration in kits was the single best predictor of POM severity ( r = -0.66). This experiment strongly supports the hypothesis that maternal immunization with PCV will reduce the burden of early infant POM and invasive pneumococcal disease.     

Immunization of newborns with bacterial conjugate vaccines

Bacterial conjugate vaccines are based on the principle of coupling immunogenic bacterial capsular polysaccharides to a carrier protein to facilitate the induction of memory T-cell responses. Following the success of Haemophilus influenzae type b conjugate vaccines in the 1980s, conjugate vaccines for Streptococcus pneumoniae and Neisseria meningitidis infections were developed and proven to be effective in protecting children against invasive disease. In this review, the use of conjugate vaccines in human newborns is discussed. Neonatal Haemophilus influenzae type b and pneumococcal conjugate vaccination schedules have been trialed and proven to be safe, with the majority of studies demonstrating no evidence for the induction of immune tolerance. Whether their neonatal administration also results in an earlier induction of clinical protection in the first 2–3 critical months of life is still to be demonstrated.     

Effectiveness of parental cocooning as a vaccination strategy to prevent pertussis infection in infants: A case-control study

BackgroundDuring a pertussis epidemic in 2009, the Department of Health, Victoria, Australia, implemented a cocoon program offering parents of new babies a funded-dose of pertussis-containing vaccine. We assessed vaccine effectiveness (VE) of the program in reducing pertussis infection in infants.MethodsUsing a matched case-control design, infants aged <12 months that were notified with pertussis between 1 January 2010 and 31 December 2011, and born during the time that the cocoon program was in place, were identified. Controls were matched by area of residence and date of birth. Telephone interviews we conducted to ascertain parents’ vaccination status, and if vaccinated, timing of vaccination receipt relative to the birth of their baby. Odds ratios (ORs) were calculated for the association between vaccination and pertussis infection, with VE calculated as (1 – OR) × 100%.ResultsThe study recruited 215 cases and 240 controls (response rates 67% and 25% of eligible participants, respectively). Vaccination of both parents after delivery of the infant and ≥28 days prior to illness onset reduced pertussis infection by 77% (Vaccine Effectiveness [VE] = 77% (confidence interval [95% CI], 18–93%). After adjusting for maternal education, presence of a sibling within the household, and the infants’ primary course vaccination status, the adjusted VE was 64% (95% CI, −58–92%).ConclusionsAlthough not reaching statistical significance, our results demonstrated that cocoon immunisation – where both parents are vaccinated in the post-partum period – may offer some protection again infant pertussis infection. Cocoon immunisation could be considered in circumstances where antenatal vaccination of the mother has not occurred.     

Varicella vaccination in Japan: necessity of implementing a routine vaccination program

Varicella-zoster virus (VZV) is the causative agent of varicella (chickenpox). It shows extremely high infectivity and is spread by airborne, droplet, and contact transmission. After a person is infected with VZV, the virus remains dormant in the dorsal root ganglia, but can be reactivated under circumstances where specific immunity declines, leading to the development of herpes zoster (shingles). Although varicella is a disease that usually resolves after about 1 week, it can cause various complications such as secondary bacterial skin infection, pneumonia, and encephalitis. In addition, varicella can become severe in immunocompromised persons, whereas VZV infection transmitted from an infected mother can cause the congenital varicella syndrome or serious neonatal varicella. In 1974, a live varicella vaccine (Oka strain) was developed in Japan for the prevention of varicella, and clinical trials performed during the development were mainly focused on high-risk children. In 1985, the Oka strain was recognized as the best varicella vaccine strain by the World Health Organization (WHO). Today, all the varicella vaccines used worldwide to immunize approximately 32 million people annually contain the Oka strain. In Japan, it has been commercially available since 1987 for the voluntary vaccination program, in which children over the age of 1 year with no history of previous varicella infection receive a single dose. In addition to healthy children, this vaccine can be used for immunocompromised children, and vaccination of elderly persons can also be done to enhance their immunity against VZV. Varicella vaccine is a highly safe vaccine with sufficient immunogenicity. The preventive effect of single-dose vaccination is believed to be approximately 80 % for all types of varicella, including mild cases; it is 95 % or greater for moderate to severe disease. Implementation of a two-dose vaccination schedule has proved to be effective against breakthrough varicella, which is observed in approximately 20–30 % of children vaccinated with a single dose. Because it is administered as part of the voluntary vaccination program, the varicella vaccination coverage rate in Japan has remained low until recently at around 20–30 %, with no sign of a decrease in the number of varicella patients. It is necessary to maintain a vaccination rate of 90 % or higher to prevent varicella epidemics. To achieve this goal, implementation of a routine vaccination program for varicella and introduction of a two-dose vaccination schedule, which is more effective than a single-dose schedule, would be highly desirable.     

Translating vaccine policy into action: A report from the Bill & Melinda Gates Foundation Consultation on the prevention of maternal and early infant influenza in resource-limited settings

Immunization of pregnant women against influenza is a promising strategy to protect the mother, fetus, and young infant from influenza-related diseases. The burden of influenza during pregnancy, the vaccine immunogenicity during this period, and the robust influenza vaccine safety database underpin recommendations that all pregnant women receive the vaccine to decrease complications of influenza disease during their pregnancies. Recent data also support maternal immunization for the additional purpose of preventing disease in the infant during the first six months of life.     

Immunization with a recombinant fusion protein protects mice against Helicobacter pylori infection

More than 50% of the world's population is infected with the bacterium Helicobacter pylori. If left untreated, infection with H. pylori can cause chronic gastritis and peptic ulcer disease, which may progress into gastric cancer. Owing to the limited efficacy of anti-H. pylori antibiotic therapy in clinical practice, the development of a protective vaccine to combat this pathogen has been a tempting goal for several years. In this study, a chimeric gene coding for the antigenic parts of H. pylori FliD, UreB, VacA, and CagL was generated and expressed in bacteria and the potential of the resulting fusion protein (rFUVL) to induce humoral and cellular immune responses and to provide protection against H. pylori infection was evaluated in mice. Three different immunization adjuvants were tested along with rFUVL: CpG oligodeoxynucleotides (CpG ODN), Addavax, and Cholera toxin subunit B. Compared to the control group that had received PBS, vaccinated mice showed significantly higher cellular recall responses and antigen-specific IgG2a, IgG1, and gastric IgA antibody titers. Importantly, rFUVL immunized mice exhibited a reduction of about three orders of magnitude in their stomach bacterial loads. Thus, adjuvanted rFUVL might be considered as a promising vaccine candidate for the control of H. pylori infection.     

2007年达州市麻疹疫苗强化免疫对麻疹流行的影响

目的评价达州市麻疹减毒活疫苗强化免疫活动对麻疹发病的影响与效果,为消除麻疹提供策略措施依据。方法2007-09对全市所有8月龄～14岁儿童在1周内集中完成MV接种1剂,3年后利用2007年MV SIAs接种资料和免疫前后麻疹发病疫情资料,应用描述流行病学方法分析麻疹发病特征并评价控制麻疹效果。结果麻疹减毒活疫苗应种儿童1 179 782人,实种儿童1 163 999人,接种率为98.66%。2007-10起麻疹发病率迅速大幅度下降,2008-2010年分别降低为0.56/10万、0.23/10万和0.54/10万,比2007年（10.41/10万）下降了94.60%以上;目标人群各年龄队列发病率2008年下降80.87%～100%且2009年继续下降,〈8月龄和〉14岁的非目标人群同时下降95.12%和86.28%～100%;削平了03/07月的发病季节高峰,分别削平和削弱了4～9岁和0～3岁的发病年龄峰值,但低水平上0～3岁发病率仍相对较高于其他年龄人群,应给予重视。结论实施8月龄～14岁儿童麻疹减毒活疫苗能快速建立整体人群免疫屏障,大幅度减少全人群麻疹发病,是消除麻疹的重要策略,麻疹减毒活疫苗3～4年内继续开展8月龄～4岁儿童后续强化免疫活动,有助于消除麻疹目标按时实现。     

Stress at three‐month immunization: Parents’ and infants’ salivary cortisol response in relation to the use of pacifier and oral glucose

The aims of the present study were to investigate (1) whether the salivary cortisol response could be dampened during a routine three‐month immunization if the infant received sweet‐tasting solution in combination with a pacifier and (2) stress experienced by parents during immunization of the infant. Ninety‐eight infants were included into one of four intervention groups: ‘glucose and pacifier’, ‘water and pacifier’, ‘glucose’, or ‘water’. Saliva was collected before and 30min after the immunization. Infants’ crying‐time and parents’ self‐reported stress (VAS) were measured before and after immunization. Infants in the ‘pacifier and glucose’ group had a significantly smaller change in salivary cortisol than infants in the other groups (F_3,72=3.1, p<0.05). In the ‘glucose and pacifier’ group the median salivary cortisol levels decreased 33% after the immunization. In the ‘water and pacifier’, ‘glucose’, and ‘water’ group median cortisol increased with 50%, 42%, and 8%, respectively. No significant differences in crying‐time were observed between the intervention groups. If the infant cried before the immunization, the crying‐time during the immunization was longer (p<0.01) and cortisol increased more (p<0.05). Median cortisol levels for parents decreased after the immunization (p<0.01). Median VAS increased 50% (p<0.0001) after immunization. First time parents rated higher stress on VAS before immunization (p<0.01). Parents’ change in cortisol and VAS were significantly related to infants’ crying time. In conclusion, the combination of oral glucose and pacifier dampen infants’ salivary cortisol in response to the three‐month immunization.     

Lymphocyte subsets in bronchoalveolar lavage after exposure to Actinobacillus pleuropneumoniae in pigs previously immunized orally or by aerosol

Young pigs were immunized with the lung-pathogenic bacterium Actinobacillus (Haemophilus) pleuropneumoniae by aerosol or orally using viable and inactivated bacteria. The cellular changes in the bronchoalveolar lavage (BAL) were studied in repeated lavages after the pigs were infected with live bacteria. The nucleated cells in the BAL were differentiated and lymphocyte subsets determined. There were no major differences between the two routes of immunization or between viable and inactivated bacteria. The immunization induced an increase in all lymphocyte subsets studied and in the appearance of plasma cells and lymphoid blasts. The infection did not cause a further increase except in granulocytes. The lack of a booster-type increase in lymphocytes in the BAL might indicate a different immunologic reaction of the lung or that lymphocytes of the BAL do not represent lung lymphocytes in general. The protective effect of the immunization might be deduced from the increase in lymphocytes after immunization but not from the reaction pattern after infection. Offprint requests to: R. Pabst