Despite the availability of live attenuated measles virus vaccines, a large number of measles-associated deaths occur among infants in developing countries during the "window of susceptibility" (age 4-9 months). During this period declining maternal antibody titers are no longer protective against wild-type measles virus (MV) and impede successful immunization with the live attenuated vaccines. Therefore, the development of a safe vaccine that would induce protective immunity in the presence of maternally derived MV-specific antibodies in young infants and would close the "window of susceptibility" is desirable. Since adenoviruses have been shown as suitable vaccine candidates capable of eliciting potent protection against mucosal infectious diseases, the ability of an adenovirus-vectored anti-measles vaccine to elicit robust immune responses against MV was assessed in this study. Mice immunized intramuscularly or intranasally with a combination of human adenovirus serotype 5 (Ad5) recombinants expressing MV hemagglutinin (H) and fusion (F) glycoproteins developed MV-specific neutralizing antibody titers similar for both routes of immunization. However, intramuscular immunization of mice with Ad5 recombinants resulted in induction of a predominant T helper type (Th1) immune response, whereas intranasal immunization induced a balanced Th1/Th2 immune response. Furthermore, intranasal immunization resulted in increased titers of MV-specific immunoglobulin A (IgA) in lungs in comparison to intramuscularly immunized animals. The ability of the Ad5 recombinants to induce protective immune responses in cotton rats by different routes of administration was also evaluated. Cotton rats that received a single dose of the Ad5 recombinants intramuscularly or intranasally experienced a rise in MV-specific neutralizing antibody titers and reduction of the viral RNA load in the lung tissue after intranasal MV challenge. In addition, the largest reduction in viral replication was observed in the group of cotton rats inoculated with the Ad5 recombinants intranasally. Based on these observations, the Ad5-based vaccine appears to be a suitable candidate against measles. Furthermore, a capability of purified globular head domain of MV H protein produced in a human cell line to induce MV-specific immune responses in mice was tested. Subcutaneous immunization of mice with the recombinant protein alone resulted in both humoral and cell-mediated immunity, characterized by the production of MV-specific serum IgG and neutralizing antibodies, as well as interferon-gamma and interleukin 5 (IL-5) production by in vitro restimulated splenocytes. The former responses were further enhanced by formulation of the protein with aluminium hydroxide. However, very low numbers of INF-gamma secreting cells and low levels of IgG2a in the serum suggested a Th2 immune response. Novel adjuvants (Th1-directing), as well as MV F protein should be considered for the inclusion into the vaccine formulations to induce more balanced Th1/Th2 immune responses against measles.

Despite the availability of live attenuated measles virus vaccines, a large number of measles-associated deaths occur among infants in developing countries during the "window of susceptibility" (age 4-9 months). During this period declining maternal antibody titers are no longer protective against wild-type measles virus (MV) and impede successful immunization with the live attenuated vaccines. Therefore, the development of a safe vaccine that would induce protective immunity in the presence of maternally derived MV-specific antibodies in young infants and would close the "window of susceptibility" is desirable. Since adenoviruses have been shown as suitable vaccine candidates capable of eliciting potent protection against mucosal infectious diseases, the ability of an adenovirus-vectored anti-measles vaccine to elicit robust immune responses against MV was assessed in this study. Mice immunized intramuscularly or intranasally with a combination of human adenovirus serotype 5 (Ad5) recombinants expressing MV hemagglutinin (H) and fusion (F) glycoproteins developed MV-specific neutralizing antibody titers similar for both routes of immunization. However, intramuscular immunization of mice with Ad5 recombinants resulted in induction of a predominant T helper type (Th1) immune response, whereas intranasal immunization induced a balanced Th1/Th2 immune response. Furthermore, intranasal immunization resulted in increased titers of MV-specific immunoglobulin A (IgA) in lungs in comparison to intramuscularly immunized animals. The ability of the Ad5 recombinants to induce protective immune responses in cotton rats by different routes of administration was also evaluated. Cotton rats that received a single dose of the Ad5 recombinants intramuscularly or intranasally experienced a rise in MV-specific neutralizing antibody titers and reduction of the viral RNA load in the lung tissue after intranasal MV challenge. In addition, the largest reduction in viral replication was observed in the group of cotton rats inoculated with the Ad5 recombinants intranasally. Based on these observations, the Ad5-based vaccine appears to be a suitable candidate against measles. Furthermore, a capability of purified globular head domain of MV H protein produced in a human cell line to induce MV-specific immune responses in mice was tested. Subcutaneous immunization of mice with the recombinant protein alone resulted in both humoral and cell-mediated immunity, characterized by the production of MV-specific serum IgG and neutralizing antibodies, as well as interferon-gamma and interleukin 5 (IL-5) production by in vitro restimulated splenocytes. The former responses were further enhanced by formulation of the protein with aluminium hydroxide. However, very low numbers of INF-gamma secreting cells and low levels of IgG2a in the serum suggested a Th2 immune response. Novel adjuvants (Th1-directing), as well as MV F protein should be considered for the inclusion into the vaccine formulations to induce more balanced Th1/Th2 immune responses against measles.

Comparison of Post-licensure safety surveillance of 13-Valent Pneumococcal Conjugate vaccine and 7-Valent Pneumococcal Conjugate vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS). Background: On February 24, 2010, Food and Drug Administration (FDA) licensed a 13-valent pneumococcal conjugate vaccine (Prevnar 13®, [PCV13]) for use among children aged 6 weeks--71 months. The Advisory Committee on Immunization Practices (ACIP) recommended PCV13 routine vaccination of all children aged 2--59 months, children aged 60--71 months with underlying medical conditions, with PCV13 replacing PCV7 for all doses. Methods: We searched case reports to the Vaccine Adverse Event Reporting System (VAERS), a US passive surveillance system, for adverse events (AEs) reported after immunization with PCV13 vaccine from February 24, 2010 through February 24, 2011 for persons vaccinated from February 24, 2010 through December 31, 2010 and compared them with AEs reported by persons who were vaccinated with PCV7. Results: VAERS received 1503 reports of AEs after PCV13; multiple vaccines were given in 79.0% of reports. One hundred eighty (11.9%) were coded as serious, including nineteen reports of death. The most frequently reported symptoms were injection site reactions, fever, irritability and vomiting. Seven hundred fifty-eight (50.4%) reports comprised males. Most reports (37.7%) were from children 1-2 years. Total number of reports received for PCV13 was very similar to those received after vaccination with PCV7. Conclusions: AEs reported to VAERS following 13-valent pneumococcal conjugate vaccine were consistent with AEs previously observed in pre-licensure trials. We did not identify any major safety concerns or outcomes.

The purpose of this project is to develop a clinical practice guideline with recommendations for vaccination and vaccine hesitancy in the pediatric setting. Routine vaccinations are given to children at recommended ages to decrease the incidence of, and prevent infectious disease. These vaccinations prevent diseases such as rotavirus, diphtheria, pertussis, tetanus, hepatitis B, haemophilus influenza type B, pneumococcal disease, polio, influenza, measles, mumps, rubella, varicella and hepatitis A. There are currently no guidelines that combine evidence-based interventions to increase vaccination rates, the recommended vaccine schedule, specific information on each vaccination, its side effects, and ingredients of each vaccination. By developing this guideline, it is hoped that pediatric providers will be able to effectively approach the caregivers of vaccine-aged children with evidence based information about vaccination, and be able to address specific concerns regarding vaccines. The available literature was formally evaluated using GRADEpro software. These results were put into the BRIDGE-Wiz (Building Recommendations in a Developer ’s Guideline Editor) software to create clear, concise, key action statements for the guideline. There were five recommendations that were created based on the literature review which include assessing parental concerns regarding vaccination at each visit, educating parents on vaccination, each vaccine, at each visit and when concerns arise, recommending vaccinations during each visit and when the opportunity arises, recommending pre-scheduling vaccination appointments, and implementing a reminder/recall system when vaccinations are due or past due. There were also informational tables created for provider reference that include important information regarding vaccines. The first table includes each vaccination, the disease it prevents, and the risk of the disease vs the risk of the vaccination. The second table includes the vaccine ingredients that commonly cause concern, and information to address those concerns. The guideline can be used in pediatric primary care to guide interventions to increase the uptake of vaccinations, and as a tool for providers to use while educating parents on specific vaccinations. The guideline was formally evaluated using the AGREE II tool by three experts in the field of pediatric primary care. All three of the reviewers stated that they would recommend the guideline for use in the pediatric setting.

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