NOVEL MECHANISMS OF ANTIGEN PROCESSING THAT ENHANCE BCG VACCINE EFFICACY

Mycobacterium tuberculosis, the causative agent of tuberculosis, is the most lethal single infectious agent afflicting man today causing 2 million deaths per year. The World Health Organization recommends a vaccine as the best option to prevent this disease. The current vaccine, BCG, has a variable efficacy and does not protect adults. It is known that BCG vaccine becomes sequestered in special phagosome compartments of macrophages that do not fuse with lysosomes. Since lysosome fusion is necessary for peptide production and T cell priming leading to protective TH1 immunity, we hypothesized that vaccine efficacy is reduced and occurs perhaps due to non-lysosome dependent mechanisms. We therefore proposed an in depth analysis of phagosome environment, and its proteome to unravel mechanisms of antigen processing and presentation. We initially discovered that three mechanisms of pH regulation including vacuolar proton ATPase, phagocyte oxidase and superoxide dismutase (SOD) secretion from BCG vaccine affect antigen processing within phagosomes. These studies led to the discovery that a mutant of BCG vaccine which lacked SOD was a better vaccine. Subsequently, the proteomic analysis of vaccine phagosomes led to the discovery of novel protease (γ-secretase) enriched on BCG vaccine phagosomes. We then demonstrated that these proteases generated a peptide from the BCG vaccine which was presented through the MHC-II pathway to T cells and induced a TH1 response. The specificity of antigen production from γ-secretase was confirmed through siRNA knockdown of the components of the protease namely, nicastrin, presenilin and APH, which led to a decrease in antigen presentation. We therefore conclude that, even though BCG phagosomes are sequestered and do not fuse with lysosomes to generate peptide antigens, there are complex and novel in situ mechanisms within phagosomes that are capable of generating an immune response. We conclude that TH1 immunity to BCG vaccine arises mostly due to non-lysosome dependent immune mechanisms of macrophages and dendritic cells.

Development of a protective vaccine against Helicobacter pylori

Helicobacter pylori, which colonizes the stomach and causes the most common chronic infection in man, is associated with peptic ulceration, gastric carcinoma and gastric lymphoma. Studies in animals demonstrated that mucosal immunization could induce immune response against H. pylori and prevent H. pylori infection only if powerful mucosal adjuvants such as cholera toxin (CT) or heat-labile toxin of E. coli (LT) were used along with an H. pylori protein antigen. Adjuvants such as CT or LT cannot be used for humans because of their toxicity. Finding non-toxic alternative adjuvants/immunomodulators or immunization strategies that eliminates the use of adjuvants is critical for the development of efficacious human Helicobacter vaccines. We investigated whether several new adjuvants such as Muramyl Tripeptide Phosphatidylethonolamine (MTP-PE), QS21 (a Quil A derivative), Monophosphoryl lipid A (MPL) or heat shock proteins (HSP) of Mycobacterium tuberculosis could be feasible to develop a safe and effective mucosal vaccine against H. pylori using a murine model. C57/BL6 mice were immunized with liposomes incorporating each adjuvant along with urease, a major antigenic protein of H. pylori, to test their mucosal effectiveness. Since DNA vaccination eliminates both the use of adjuvants and antigens we also investigated whether immunization with plasmid DNA encoding urease could induce protective immunity to H. pylori infection in the same murine model. We found that oral vaccination with liposomal MTP-PE (6.7 m g) and urease, (100 m g) induced antigen-specific systemic and mucosal immune response and protected mice against H. pylori challenge when compared to control groups. Parenteral and mucosal immunizations with as little as 20 m g naked or formulated DNA encoding urease induced systemic and mucosal immune response against urease and partially protected mice against H. pylori infection. DNA vaccination provided long-lasting immunity and serum anti-urease IgG antibodies were elevated for up to 12 months. No toxicity was detected after immunizations with either liposomal MTP-PE and urease or plasmid DNA and both were well tolerated. We conclude that immunization liposomes containing MTP-PE and urease is a promising strategy deserving further investigation and may be considered for humans. DNA vaccination could be used to prime immune response prior to oral protein vaccination and may reduce the dose of protein and adjuvant needed to achieve protective immunity. ^

Prime and boost vaccination against HER2/neu in breast cancer

Breast cancer is the most common cancer among women with approximately 180,000 new cases being diagnosed yearly in the United States (1). HER2/neu gene amplification and subsequent protein overexpression is found in 20–30% of breast cancer patients and can lead to the promotion of various metastasis-related properties (2–4) and/or resistance to cancer therapies such as chemotherapy and radiation (5). ^ The protein product of the HER2/neu gene, p185, is a proven target for immunological therapy. Recently, passive immunotherapy with the monoclonal antibody Trastuzumab® has validated an immunological approach to HER2/neu+ breast cancer. Immunity to HER2/ neu, when found in breast cancer patients, is of low magnitude. Vaccination-induced HER2/neu-specific antibodies and HER2/neu-specific cytotoxic T cells could result in long-lived immunity with therapeutic benefit. Many features of DNA vaccines and attenuated viral vectors may contribute to the efficacy of prime-boost vaccination. In particular, vaccines capable of eliciting strong cell-mediated immunity are thought to hold the greatest promise for control of cancer (6–9). ^ To optimize cellular immunization to HER2/neu in my study, the HER2/neu gene was presented to the immune system using a priming vector followed by a second vector used as the boost. In both animals and humans, priming with DNA and boosting with a poxviruses, vaccinia or canarypox appears to be particularly promising for induction of a broad immune responses (10). ^ I tested three gene vaccines encoding the HER2/neu gene: (1) a plasmid, SINCP, that contains part of the genome of Sindbis virus; (2) Viral Replicon Particles (VRP) of Venezuela Equine Encephalitis virus (VEE) and (3) E1/E2a-deleted human Type 5 Adenovirus. In SINCP and the VRP, the caspid and envelope genes of the virus were deleted and replaced with the gene for HER2/neu. SINCP-neu, VRP- neu and Adeno-neu when used alone were effective vaccines protecting healthy mice from challenge with a breast cancer cell line injected in the mammary fat pad or injected i.v. to induce experimental lung metastasis. However, SINCP-neu, VRP-neu or Adeno-neu when used alone were not able to prolong survival of mice in therapeutic models in which vaccination occurred after injection of a breast cancer cell line. ^ When the vaccines were combined in a mixed regimen of a SINCP- neu prime VRP-neu or Adeno-neu boost, there was a significant difference in tumor growth and survival in the therapeutic vaccine models. In vitro assays demonstrated that vaccination with each of the three vaccines induced IgG specific for p185, the gene product of HER2/neu, induced p185-specific T lymphocytes, as measured by tetramer analysis. Vaccination also induced intracellular INF-γ and a positive ELISPOT assay. These findings indicate that SINCP-neu, VRP-neu and Adeno-neu, used alone or in combination, may have clinical potential as adjuvant immunotherapy for the treatment of HER2/neu-expressing tumors. ^

Lactoferrin: An adjuvant to enhance the efficacy of the BCG vaccine

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world's population. The established vaccine for TB; an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed virtually unchanged since 1921. Intensive research is focused on developing a TB vaccine that can surpass and improve the existing BCG vaccine. Lactoferrin, an iron binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine. Specifically, Lactoferrin enhanced the ratio of IL-12:IL-10 production from macrophages stimulated with LFS or infected with BCG, indicating the potential to affect T-cell development in vivo. Five different vaccination protocols were investigated for generation of host protective responses against MTB infection using Lactoferrin admixed to the BCG vaccine. Mice immunized and boosted at 2 weeks with BCG/Lactofefrin increased host protection against MTB infection by decreasing organ bacterial load and reducing lung histopathology. The observed postchallenge results paralleled with increasing production of IFN-γ, IL-2, TNF-α, and IL-12 from BCG stimulated splenocytes. In vitro studies examined possible mechanisms of Lactoferrin action on BCG infected macrophages and dendritic cells. Addition of Lactoferrin to BCG infected macrophages and dendritic cells increased stimulation of presensitized CD3+ and CD4+ T-cells. Analysis by fluorescent activated cell sorting (FACS) revealed an increase in surface expression of MHC I and decreased ratio of CD80/86 from BCG infected macrophages cultured with Lactoferrin. In contrast, Lactoferrin decreased surface expression of MHC I, MHC II, CD80, CD86, and CD40, but increased CD 11c, from BCG infected dendritic cells, indicating involvement of adhesion molecules. Overall, these studies indicate that Lactoferrin is a useful and effective adjuvant to improve efficacy of the BCG vaccine by enhancing generation of mycobacterial antigen specific T-cell responses through promotion of antigen presentation and T-cell stimulation.^

Influenza vaccination and peoples' knowledge and attitudes towards it: Factors that influenced influenza vaccination during the 2004--2005 influenza vaccine shortage

Influenza and pneumonia together comprise the seventh leading cause of death among adults in the U.S and were responsible for 65,163 deaths in 2003 and an average of 36,000 deaths per year in the United States from 1990 to 1999. Vaccination is efficacious and cost-effective in terms of preventing the infection and reducing both health care costs and productivity losses associated with influenza illness. The vaccine shortage of 2004–2005 resulted in a 39% decrease in the influenza vaccine supplies. During the fall of 2004, we conducted a nationwide, random-digit dialing, telephonic-interview survey of 1,202 adults aged 18 years and older to ascertain influenza vaccine knowledge, attitude and behavior. Of the 1,202 total interviewed subjects, 44.7% had received or intended to receive vaccine at the time of the survey (2004–05) and 39.6% had received the influenza vaccine the previous year (2003–04). Receipt of vaccine increased with previous receipt of the influenza vaccine (OR 13.17, 95% CI 8.65–20.08), increased motivation status (OR 7.58, 95% CI 4.03–14.25), subjective risk status (OR 3.33, 95% CI 2.23–4.97), age (OR 1.83, 95% CI 1.22–2.75) and previous receipt of the pneumococcal vaccine (OR 1.75, 95% CI 1.02–3.0). The influenza vaccine shortage of 2004–05 did not have a negative impact on the vaccination rates of study population. In addition to the increased rates, a large majority of respondents were also aware of the shortage of influenza vaccine during the 2004–05 season, about the indications for receiving the influenza vaccine, about alternative methods to prevent contracting the influenza and increased motivation to receive the vaccine. ^

Alpha C protein of group B Streptococcus as a potential vaccine candidate

Group B Streptococcus (GBS) is a leading cause of life-threatening infection in neonates and young infants, pregnant women, and non-pregnant adults with underlying medical conditions. Immunization has theoretical potential to prevent significant morbidity and mortality from GBS disease. Alpha C protein (α C), found in 70% of non-type III capsule polysaccharide group B Streptococcus, elicits antibodies protective against α C-expressing strains in experimental animals and is an appealing carrier for a GBS conjugate vaccine. We determined whether natural exposure to α C elicits antibodies in women and if high maternal α C-specific serum antibody at delivery is associated with protection against neonatal disease. An ELISA was designed to measure α C-specific IgM and IgG in human sera. A case-control design (1:3 ratio) was used to match α C-expressing GBS colonized and non-colonized women by age and compare quantified serum α C-specific IgM and IgG. Sera also were analyzed from bacteremic neonates and their mothers and from women with invasive GBS disease. Antibody concentrations were compared using t-tests on log-transformed data. Geometric mean concentrations of α C-specific IgM and IgG were similar in sera from 58 α C strain colonized and 174 age-matched non-colonized women (IgG 245 and 313 ng/ml; IgM 257 and 229 ng/ml, respectively). Delivery sera from mothers of 42 neonates with GBS α C sepsis had similar concentrations of α C-specific IgM (245 ng/ml) and IgG (371 ng/ml), but acute sera from 13 women with invasive α C-expressing GBS infection had significantly higher concentrations (IgM 383 and IgG 476 ng/ml [p=0.036 and 0.038, respectively]). Convalescent sera from 5 of these women 16-49 days later had high α C-specific IgM and IgG concentrations (1355 and 4173 ng/ml, respectively). In vitro killing of α C-expressing GBS correlated with total α C-specific antibody concentration. Invasive disease but not colonization elicits α C-specific IgM and IgG in adults. Whether α C-specific IgG induced by vaccine would protect against disease in neonates merits further investigation. ^

Health beliefs and attitudes of HPV among Hispanic parents as predictors of intention to use the HPV vaccine

Human Papillomavirus (HPV) is the most common sexually transmitted disease in the United States. Although HPV prevalence is high in the United States, there are a limited number of research studies that focus on Hispanics, who have higher incidence rates of cervical cancer than their non-Hispanic counterparts. The HPV vaccine introduced in 2006 may offer a feasible solution to the issues surrounding high prevalence of HPV. Due to the high prevalence of HPV infection among adolescents and young adults it has been suggested that HPV vaccination begin prior to onset sexual activity and focus on non-sexually active adolescents and pre-adolescents. Consequently, it has become increasingly important to assess knowledge and awareness of HPV in order to develop effective intervention strategies. This pilot study evaluated the knowledge and health beliefs of Hispanic parents regarding HPV and the HPV vaccine using a newly developed questionnaire based on the constructs of the Health Belief Model. The sample was recruited from an ob-gyn office in El Paso, Texas. Descriptive data show that the majority of the sample was female (94.1%), Hispanic (76.5%), Catholic (64.7%), and had at least a high school education (55.9%). Chi-square analysis revealed that the following variables differed amongst parents who intended to vaccinate their child against HPV and those who did not: religion (p=0.038), perceived severity item "HPV infections are easily treated" (p=0.052), perceived benefits item "It is better to vaccinate a child against an STI before they become sexually active" (p=0.014) and perceived barriers item "The HPV vaccine may have serious side effects that could harm my child" (p=0.004). Univariate logistic regression indicated that religion (OR = 4.8, CI: 1.04, 21.8) and "The HPV vaccine may have serious side effects that could harm my child" (OR = 15.9, CI: 1.73, 145.8) were significant predictors of parental intention to vaccinate. Multivariate logistic regression, using backwards elimination, indicated that religion (OR = 7.7, CI: 1.25, 47.8) and "The HPV vaccine may have serious side effects that may harm my child" (OR = 7.6, CI: 1.15, 50.2) were the best predictive variables for parental intention to vaccinate. ^

Behavioral cognitions and factors related to hepatitis B vaccine acceptance and compliance in a cohort of drug users in Houston, Texas

Purpose. Drug users are a large group of those at highest risk for contracting Hepatitis B (HBV). This study sought to identify predictors of HBV vaccine acceptance and compliance in a cohort of current drug users in Houston, Texas. Perceived severity of HBV, perceived risk of HBV, perceived peer support of HBV vaccine, and perceived benefits of HBV vaccine were also examined assess their relationship to HBV compliance. ^ Methods. A randomized intervention study was conducted in a cohort of current drug users in Houston, Texas. Participants were recruited by community outreach workers from two urban neighborhoods in Houston known for high drug use. Participants were randomized to a standard vaccine schedule group or an accelerated vaccine schedule group. Participants were also randomized to either a standard behavioral intervention group or an enhanced behavioral intervention group designed to increase HBV vaccine acceptance and compliance. Baseline visits included an interview for demographic factors, drug and sexual behaviors, and HBV beliefs; and participants received the first dose of the HBV vaccine and one of the behavioral interventions. ^ Results. Of 1,643 screening participants, 77% accepted the HBV vaccine. Participants ages ≥50 were twice as likely to accept the vaccine. African Americans and less frequent drug users were also significantly more likely to accept the vaccine. Of the 1,259 participants who enrolled in the study, 75% were compliant to the HBV vaccine. Predictors of compliance were found to be race, housing status, and alcohol use. Speedball users were found to be 74% less likely to be compliant the HBV vaccine. None of the behavioral constructs assessed were found to significantly predict HBV compliance. However, additional analyses found that there were significant changes in mean scores of the behavioral concepts when measured at six month follow-up. ^ Conclusion. Results from this study indicate that when offered a free vaccine in the drug user community, a large percentage will be compliant to the vaccine series. The behavioral cognitions commonly used in HBV compliance research need to be extended to accurately fit this cohort. Also, vaccine intervention focus needs to be on reaching the homeless segment of the drug users and the speedball users. ^

Comparison of compliance and immune response of drug users on the standard and accelerated hepatitis B vaccine schedules - Houston, Texas

Despite the availability of hepatitis B vaccine for over two decades, drug users and other high-risk adult populations have experienced low vaccine coverage. Poor compliance has limited efforts to reduce transmission of hepatitis B infection in this population. Evidence suggests that immunological response in drug users is impaired compared to the general population, both in terms of lower seroprotection rates and antibodies levels.^ The current study investigated the effectiveness of the multi-dose hepatitis B vaccine and compared the effect of the standard and accelerated vaccine schedules in a not-in-treatment, drug-using adult population in the city of Houston, USA.^ A population of drug-users from two communities in Houston, susceptible to hepatitis B, was sampled by outreach workers and referral methodology. Subjects were randomized either to the standard hepatitis vaccine schedule (0, 1-, 6-month) or to an accelerated schedule (0, 1-, 2-month). Antibody levels were detected through laboratory analyses at various time-points. The participants were followed for two years and seroconversion rates were calculated to determine immune response.^ A four percent difference in the overall compliance rate was observed between the standard (73%) and accelerated schedules (77%). Logistic regression analyses showed that drug users living on the streets were twice as likely to not complete all three vaccine doses (p=0.028), and current speedball use was also associated with non-completion (p=0.002). Completion of all three vaccinations in the multivariate analysis was also correlated with older age. Drug users on the accelerated schedule were 26% more likely to achieve completion, although this factor was marginally significant (p=0.085).^ Cumulative adequate protective response was gained by 65% of the HBV susceptible subgroup by 12-months and was identical for both the standard and accelerated schedules. Excess protective response (>=100 mIU/mL) occurred with greater frequency at the later period for the standard schedule (36% at 12-months compared to 14% at six months), while the greater proportion of excess protective response for the accelerated schedule occurred earlier (34% at 6 months compared to 18% at 12-months). Seroconversion at the adequate protective response level of 10 mIU/mL was reached by the accelerated schedule group at a quicker rate (62% vs. 49%), and with a higher mean titer (104.8 vs. 64.3 mIU/mL), when measured at six months. Multivariate analyses indicated a 63% increased risk of non-response for older age and confirmed the existence of an accelerating decline in immune response to vaccination manifesting after 40 years (p=0.001). Injecting more than daily was also highly associated with the risk of non-response (p=0.016).^ The substantial increase in the seroprotection rate at six months may be worth the trade-off against the faster antibody titer decrease and is recommended for enhancing compliance and seroconversion. Utilization of the accelerated schedule with the primary objective of increasing compliance and seroconversion rates during the six months after the first dose may confer early protective immunity and reduce the HBV vulnerability of drug users who continue, or have recently initiated, increased high risk drug use and sexual behaviors.^

Role of T cell response during vaccine immunity to tuberculosis

Tuberculosis remains one of the leading causes of death in man due to a single infectious agent. An estimated one-third of the world's population is infected with the causative agent, Mycobacterium tuberculosis (Mtb), despite the availability of the widely used vaccine, BCG. BCG has significantly varying protection rates with the lowest level of protection seen with the most common form of TB, adult pulmonary TB. Thus, numerous studies are being conducted to develop a more efficient vaccine. The ideal candidate vaccine would possess the ability to induce a solid and strong Th1 response, as this is the subset of T cells primarily involved in clearance of the infection. A novel vaccine should also induce such a response that may be recalled and expanded upon subsequent infection. Our group has introduced a mutant of a virulent strain of Mtb which lacks a component of the immunogenic antigen 85 complex (Ag85). Our vaccine, ΔfbpA, does not secrete the fibronectin binding protein Ag85A, and this has shown to lead to its attenuation in both murine macrophages and mice. Previous studies have also proven that ΔfbpA is more protective in mice than BCG against virulent aerosol challenge with Mtb. This study addresses the mechanisms of protection observed with ΔfbpA by phenotyping responding T cells. We first evaluated the ability of dendritic cells to present the mycobacteria to naïve T cells, an in vitro mock of primary immunization. We also measured the response of primed T cells to macrophage-presented mycobacteria to interpret the possible response of a vaccinated host to a boost. We concluded that ΔfbpA can elicit a stronger Th1 response compared to BCG in vitro, and further observed that this enhanced response is at least partly due to the presence of proteins encoded by a region of the genome absent in all strains of BCG. Finally, we observed this heightened Th1 response in the mouse model after primary vaccination and a virulent aerosol challenge. The cytolytic T cell response was also measured after virulent challenge and was found to be superior in the ΔfbpA-treated group when compared to the BCG group. ^

A retrospective cohort study of the duration of hepatitis B vaccine immunity and associated factors in pediatric dialysis patients

Dialysis patients are at high risk for hepatitis B infection, which is a serious but preventable disease. Prevention strategies include the administration of the hepatitis B vaccine. Dialysis patients have been noted to have a poor immune response to the vaccine and lose immunity more rapidly. The long term immunogenicity of the hepatitis B vaccine has not been well defined in pediatric dialysis patients especially if administered during infancy as a routine childhood immunization.^ Purpose. The aim of this study was to determine the median duration of hepatitis B immunity and to study the effect of vaccination timing and other cofactors on the duration of hepatitis B immunity in pediatric dialysis patients.^ Methods. Duration of hepatitis B immunity was determined by Kaplan-Meier survival analysis. Comparison of stratified survival analysis was performed using log-rank analysis. Multivariate analysis by Cox regression was used to estimate hazard ratios for the effect of timing of vaccine administration and other covariates on the duration of hepatitis B immunity.^ Results. 193 patients (163 incident patients) had complete data available for analysis. Mean age was 11.2±5.8 years and mean ESRD duration was 59.3±97.8 months. Kaplan-Meier analysis showed that the total median overall duration of immunity (since the time of the primary vaccine series) was 112.7 months (95% CI: 96.6, 124.4), whereas the median overall duration of immunity for incident patients was 106.3 months (95% CI: 93.93, 124.44). Incident patients had a median dialysis duration of hepatitis B immunity equal to 37.1 months (95% CI: 24.16, 72.26). Multivariate adjusted analysis showed that there was a significant difference between patients based on the timing of hepatitis B vaccination administration (p<0.001). Patients immunized after the start of dialysis had a hazard ratio of 6.13 (2.87, 13.08) for loss of hepatitis B immunity compared to patients immunized as infants (p<0.001).^ Conclusion. This study confirms that patients immunized after dialysis onset have an overall shorter duration of hepatitis B immunity as measured by hepatitis B antibody titers and after the start of dialysis, protective antibody titer levels in pediatric dialysis patients wane rapidly compared to healthy children.^

Lessons learned from nationwide vaccine programs: Comparing human papillomavirus, poliomyelitis vaccine, and swine flu

This assessment compares the human papillomavirus (HPV) nationwide vaccine to the poliomyelitis vaccine and the swine flu vaccine with the purpose of finding parallels and lessons in the controversies faced by the development and use of the vaccines. There are a number of great barriers that are facing the HPV vaccine to date. These controversies lie in dealing with the risk involved in taking the vaccine, how much control the government should have in administering the vaccine, how to communicate the risk to the public, and the cost-effectiveness of the vaccine versus treatment for cervical cancer. The lessons for the HPV vaccine that were learned after comparison and assessment of the controversies were: (1) plan ahead of time on how to inform the public if a risk develops from taking the HPV vaccination and it may be better to provide some information while the event is occurring, always being as truthful as possible, and later dispensing more information once all of the facts are known, (2) the human papillomavirus is not something that will become a pandemic in a short amount of time because the virus takes a long time to develop into cervical cancer, so if a major risk begins to show after continuing to develop and administer the vaccine for an amount of time, it may be better to take it off the market for a while and possibly reconfigure it to help eliminate some of the risks, (3) if side reactions and risks do develop and the government assumes liability for these reactions, the cost-effectiveness can be greatly affected, so it is important to be constantly checking to see if all the monetary and health benefits of the vaccine are outweighing any of the negative costs of the vaccine, and lastly, (4) the public must feel that every aspect of the vaccine, both good and bad, has been thought over and the benefits of taking the vaccine prevail over the negatives and that politics and commercial interests have nothing to do with the production and administration of the vaccine. ^

Quality assurance plan for a vaccine preventable diseases surveillance program

Public health surveillance programs for vaccine preventable diseases (VPD) need functional quality assurance (QA) in order to operate with high quality activities to prevent preventable communicable diseases from spreading in the community. Having a functional QA plan can assure the performance and quality of a program without putting excessive stress on the resources. A functional QA plan acts as a check on the quality of day-to-day activities performed by the VPD surveillance program while also providing data that would be useful for evaluating the program. This study developed a QA plan that involves collection, collation, analysis and reporting of information based on standardized (predetermined) formats and indicators as an integral part of routine work for the vaccine preventable disease surveillance program at the City of Houston Department of Health and Human Services. The QA plan also provides sampling and analysis plans for assessing various QA indicators, as well as recommendations to the Houston Department of Health and Humans Services for implementation of the QA plan. The QA plan developed for VPD surveillance in the City of Houston is intended to be a low cost system that could serve as a template for QA plans as part of other public health programs not only in the city or the nation, but could be adapted for use anywhere across the globe. Having a QA plan for VPD surveillance in the City of Houston would serve well for the funding agencies like the CDC by assuring that the resources are being expended efficiently, while achieving the real goal of positively impacting the health and lives of the recipient/target population. ^

An analysis of Texas's school based HPV vaccine mandate: A public health risk communication failure: HPVETO!

Genital human papillomavirus (HPV) is of public health concern because persistent infection with certain HPV types can cause cervical cancer. In response to a nationwide push for cervical cancer legislation, Texas Governor Rick Perry bypassed the traditional legislative process and issued an executive order mandating compulsory HPV vaccinations for all female public school students prior to their entrance in the sixth grade. By bypassing the legislative process Governor Perry did not effectively mitigate the risk perception issues that arose around the need for and usefulness of the vaccine mandate. This policy paper uses a social policy paradigm to identify perception as the key intervening factor on how the public responds to risk information. To demonstrate how the HPV mandate failed, it analyzes four factors, economics, politics, knowledge and culture, that shape perception and influence the public's response. By understanding the factors that influence the public's perception, public health practitioners and policy makers can more effectively create preventive health policy at the state level. ^