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. ^

Mechanisms involved in suppression of the elicitation of immune responses by ultraviolet light

The ultraviolet radiation (UVR) present in sunlight is the primary cause of nonmelanoma skin cancer and has been implicated in the development of cutaneous malignant melanoma. Ultraviolet radiation also suppresses the immune response. In the majority of studies investigating the mechanisms regulating UV-induced immune suppression, UV is used to suppress the induction of immune responses. Equally important, is the ability of UVR to suppress established immune responses, such as the recall reaction in humans, which protects against microbial infections. We established a murine model to help elucidate the immunological mechanisms governing UV-induced suppression of the elicitation of immune responses. 80 kJ/m2 of UVR nine days after sensitization consistently suppressed the elicitation of delayed type hypersensitivity reaction to C. albicans . We found ultraviolet A (320±400 nm) radiation was as effective as solar-simulated ultraviolet A + B (290±400 nm) in suppressing the elicitation of an established immune response. The mechanisms involved in UV-induced suppression of the induction & elicitation of the immune response are similar. For example, mice irradiated with UV after immunization generated antigen-specific T suppressor cells. Injection of monoclonal antibodies to IL-10 or recombinant IL-12 immediately after exposure to UVR blocked immune suppression. Liposomes containing bacteriophage T4N5 to the skin of mice also prevented immune suppression, demonstrating an essential role for ultraviolet-induced DNA damage in the suppression of established immune reactions. ^ In addition to damaging DNA, UV initiates immune suppression through the isomerization of urocanic acid in the epidermis. Here we provide evidence that cis-UCA induces systemic immunosuppression via the serotonin (5-hydroxyyryptamine; 5-HT) receptor. Biochemical and immunological analysis indicate that cis-UCA binds to, and activates, the serotonin receptor. Moreover, serotonin specific antibodies block UV- and/or cis-UCA-induced immune suppression. Our findings identify cis-UCA as novel serotonin receptor ligand and indicate that serotonin receptor engagement can activate immune suppression. Cumulatively, our data suggest that similar immune regulatory mechanisms are activated regardless of whether we expose mice to solar-simulated UV (UVA + UVB) radiation or UVA only, and that ultraviolet radiation activates similar immunologic pathways to suppress the induction or the elicitation of the immune response. ^

Survey of VFC provider knowledge of catch-up regimens and contraindications to vaccination in Houston, Texas

In 2004, Houston had one of the lowest childhood immunization levels among major metropolitan cities in the United States at 65% for the 4:3:1:3:3 vaccination series. Delays in the receipt of scheduled vaccinations may be related to missed opportunities due to health care provider lack of knowledge about catch-up regimens and contraindications for pediatric vaccination. The objectives of this study are to identify, measure, and report on VFC provider-practice characteristics, knowledge of catch-up regimens and contraindications, and use of Reminder recall (R/R) and moved or gone elsewhere (MOGE) practices among providers with high (>80%) and low (<70%) immunization coverage among 19-35 month old children. The sampling frame consists of 187 Vaccines for Children (VFC) providers with 2004 clinic assessment software application (CASA) scores. Data were collected by personal interview with each participating practice provider. Only ten VFC providers were successful at maximizing vaccinations for every vignette and no provider administered the maximum possible number of vaccinations at visit 2 for all six vignettes. Both coverage groups administered polio conjugate vaccine (PCV), haemophilus influenza type b (Hib), and diphtheria, tetanus and acellular pertussis (DTaP) most frequently and omitted most frequently varicella zoster vaccine (VZV) and measles, mumps, and rubella (MMR) vaccine. ^

Catalytic antibody response to the Staphylococcus aureus virulence factor Efb

Staphylococcus aureus is a globally prevalent pathogen that can cause a wide variety of acute and chronic diseases in both adults and children, in both immune susceptible populations and healthy individuals. Its ability to cause persistent infections has been linked to multiple immune evasion strategies, including Efb-mediated complement inhibition. As new multi-drug-resistant strains emerge, therapeutic alternatives to traditional antibiotics must be developed. These experiments assessed the ability of healthy patient immunoglobulin to cleave Efb and disable the complement-inhibitory properties of Efb in vitro. Levels of immunoglobulin-mediated Efb catalysis varied both between immunoglobulin isoform/isotype and between individuals. Serum IgG showed the strongest catalytic activity of the immunoglobulin isotypes tested. Additionally, IgG hydrolyzed the virulence factor in a way that enabled only minimal binding to the complement component C3b, effectively blocking Efb-mediated inhibition of complement lysis. Salivary IgA and serum IgM did not block Efb-mediated inhibition of complement. Catalytic IgG selectively cleaved Efb and showed no cleavage of a variety of other proteins tested. Catalytic activity of IgG was inhibited by serine protease inhibitors, but not by other protease inhibitors, suggesting a serine-protease mechanism of catalysis. It is proposed that varying concentrations and activity levels of catalytic IgG between healthy individuals and those with current or recurrent S. aureus infections in both adult and pediatric populations be studied in order to assess the potential effectiveness of passive immunization therapy with catalytic monoclonal IgG. ^

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. ^

Characterization of humoral immune responses against Treponema pallidum antigens

The spirochete Treponema pallidum subsp. pallidum is the causative agent of syphilis, a sexually transmitted disease with an estimated 12 million new cases per year worldwide. There is no vaccine currently available for the prevention of syphilis. In the present study, the T. pallidum hypothetical protein TP0693 was examined to determine its cellular location, and its potential for use as a vaccine candidate and immunodiagnostic for syphilis. TP0693 was demonstrated to be strongly reactive with sera from rabbits infected experimentally with T. pallidum for >25 days. Results from proteinase K digestion, immunofluorescence and immunoelectron microscopy were consistent with outer surface localization of TP0693. Serum reactivity against TP0693 was detected in only 68% of syphilis patients, which does not support its use as an immunodiagnostic for syphilis. Immunization of rabbits with TP0693 or three other outer membrane candidates did not alter the course of lesion development atter T. pallidum inoculation. We also examined the T. pallidum proteome by two-dimensional gel electrophoresis coupled with mass spectrometry analysis and immunoblotting. This approach resulted in the identification of 95 unique polypeptides, several of which were reactive with sera from infected rabbits and syphilis patients. The analyses described here enabled us to identify antigens potentially useful as vaccine candidates or diagnostic markers, and may provide insight into host-pathogen interactions during T. pallidum infection. ^

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.^

Use of pneumococcal vaccine in people with chronic disease in United States

Objective. The risk of complications and deaths related to pneumococcal infections is high among high risk population (i.e. those with chronic diseases such as diabetes or asthma), despite current immunization recommendations. The aim of this study is to evaluate the use of pneumonia vaccine in adults with and without diabetes or asthma by year of age and whether immunization practices conform to policy recommendations. ^ Methods. Data were drawn from 2005 Behavioral Risk Factor Surveillance Study. Age specific estimated counts and proportions of pneumonia vaccination status were computed. The association of socio-demographic factors with vaccination status was estimated from multiple logistic regression and results were presented for adults (18-64yrs) and elderly (65 or older). ^ Results. Overall 12.3% of the adults and 61.5% of elderly reported ever received pneumonia vaccine. 66.8% of diabetics and 72.6% of asthmatics received the vaccine among elderly. 33.4% of diabetics and 21.6% of asthmatics received the vaccine among adults. These numbers are far away from Healthy people 2010 objective coverage rates of 90% for elderly and 60% for high risk adults. Though diabetes was one of the recommendations for the pneumonia vaccine still the status was less than 70% even at older ages. Although asthma was not an indication for pneumonia vaccine, asthmatics still achieved 50% level by an early age of 60 and reached up to 80% at as early as 75 years. In those having both asthma and diabetes, although the curve reaches to 50% level at a very early age of 40yrs, it is not stable until the age of 55 and percentages reached to as high as 90% in older ages. Odds of receiving pneumonia vaccine were high in individuals with diabetes or asthma in both the age groups. But the odds were stronger for diabetics in adults compared to those in the elderly [2.24 CI (2.08-2.42) and 1.32 CI (1.18-1.47)]. The odds were slightly higher in adults than in elderly for asthmatics [1.92 CI (1.80-2.04) and 1.73 CI (1.50-2.00)].The likelihood of vaccination also differed by gender, ethnicity, marital status, income category, having a health insurance, current employment, physician visit in last year, reporting of good to excellent health and flu vaccine status. ^ Conclusion. There is a very high proportion of high risk adults and elderly that remain unvaccinated. Given the proven efficacy and safety of vaccine there is a need for interventions targeting the barriers for under-vaccination with more emphasis on physician knowledge and practice as well as the recipient attitudes.^

Anti-glomerular basement membrane glomerulonephritis: Characterization of an epitope, antibody response, and the potential role of IL-4Ralpha in disease progression

Anti-Glomerular Basement Membrane Glomerulonephritis (anti-GBM GM) is one of the earliest described autoimmune disorders. Patients present with proteinuria, anti-GBM antibodies, and renal failure. Studies have implicated a T Helper 1 (TH1) response in disease induction and a T Helper 2 (TH2) response for disease progression. A 13 amino acid long peptide sequence spanning residues 28 through 40 [pCol(28–40)] of the Collagen IV α3 non-collagen domain (Col IV α3 NCD) is immunogenic and induces anti-GBM GN. In order to fully understand disease initiation, this peptide was further characterized. Peptides were created containing one amino acid substitution for the entire length of pCol(28–40) and induction of anti-GBM GN was monitored. When residues 31, 33, or 34 contained the substitution, anti-GBM GN was unable to be induced. Thus, residues 31, 33, and 34 of pCol(28–40) are required for induction of anti-GBM. Glomerular injury is observed as early as 14 days post anti-GBM GN induction. However, the presence of anti-GBM antibodies is not observed until 20 days post immunization. An enlarged lymph node adjacent to the diseased kidney exhibits B cell activation after renal injury and produces antibodies toward GBM. Thus, anti-GBM antibodies are a consequence of the initial renal injury. Differences between disease susceptible and disease resistant rat strains exist in the expression of IL-4Rα, a major player in the TH2 response. IL-4Rα signaling is regulated by soluble IL-4Rα (sIL-4Rα). Low expression levels of sIL-4Rα result in the stabilization of IL-4 binding, while elevated expression sequesters IL-4. Quantitative PCR experiments noted low siL-4Rα expression levels in disease susceptible rats. Induction of an immune response toward sIL-4Rα in this strain was responsible for delayed disease progression in 15 out of the 17 experimental animals. Antibody transfer and in vivo biological activity experiments confirmed that delayed disease development was due to anti-sIL-4Rα antibodies. Together these experiments indicate that a T-cell epitope is required for activation of a TH1 autoimmune response and anti-GBM antibodies are a consequence of renal injury. More importantly, a role for IL-4Rα signaling is implicated in the progression of anti-GBM GN. ^

News media coverage of policies surrounding the HPV vaccine before and after Texas Governor Rick Perry's executive order, February 2006-February 2008

Objective. In June 2006, the first vaccine for human papillomavirus (HPV) was approved by the FDA and shortly after approval, the Advisory Committee on Immunization Practices (ACIP) voted to recommend the HPV vaccine for young girls. As a result of ACIP recommendations, state legislators introduced bills to mandate the vaccine. Policies related to public health issues, such as vaccination mandates, are often influenced by news coverage of these issues. News media, particularly in times of controversies, reinforce specific messages and plays an essential role in framing issues for the public. The objective of this study is to examine the quality, content, and scope of policies for the HPV vaccine before and after Texas Governor Rick Perry issued an executive order mandating the vaccine for middle school girls.^ Methods. The Lexis-Nexis database was used to identify 335 articles on HPV vaccination mandate policies that were published in U.S. newspapers from February 1, 2006 to February 2, 2008. The coding instrument captured information about article type, main news story concern, general information about HPV, HPV vaccine mandate policies, arguments for and against HPV vaccination mandates, arguments for and against the HPV vaccine, and sources of information.^ Results. Most news articles (82.4%) occurred after Governor Rick Perry issued an executive order mandating the HPV vaccine. Most articles mentioned that HPV is sexually transmitted (90.7%) and linked HPV infection to cervical cancer (96.1%). Only 63.9% of the articles reported that the HPV vaccine protects against types of HPV that cause cervical cancer and 18.8% of the articles reported that the vaccine protects against genital warts. Only 18.2% of the news articles presented a balanced argument regarding mandatory HPV vaccinations, and only 39.4% of the news articles presented a balanced argument for the HPV vaccine.^ Conclusions. Our study revealed that news coverage regarding mandating the HPV vaccine and issues related to the vaccine itself is biased, unbalanced, and incomplete. Since the public pays a great deal of attention to health in the media, it is essential that news stories are balanced, complete, and accurate. In order to ensure that future vaccination mandates are not covered in the same way the HPV vaccination was, public health officials, health care providers and scientists should work effectively with the media to ensure that balanced information is provided.^

A systematic review of the animal and human literature on the use of vaccines to prevent dental caries

Streptococcus mutans has been identified as the primary etiological agent of human dental caries. Since its identification, there has been research focused on the development of a vaccine to prevent this disease. Preliminary research has been conducted to test both active and passive vaccines for Streptococcus mutans in animals and humans. Although a vaccine for dental caries caused by Streptococcus mutans would most likely be administered to children, no testing of any type of dental caries vaccines has been conducted on children as of yet. The public health imperative for the development of a vaccine is great. Not only will a vaccine reduce the various consequences, but it would also improve quality of life for many individuals. Among the many possible vaccine antigen candidates, researchers have also been focusing on protein antigens, GTFs, and Gbps as possible candidates for a vaccine. There are also many routes of administration under research, with topical, oral, and intranasal showing a lot of promise. This review will provide an overview on the current state of research, present key factors influencing prevalence of caries, and summarize and discuss the results of animal and human studies on caries vaccines against Streptococcus mutans. The progress and obstacles facing the development of a vaccine to fight dental caries will also be discussed. ^

Mandating the HPV vaccine

Background. HPV is the underlying cause of cervical cancer, a malignant tumor of the female genital tract. Each year, cervical cancer is newly diagnosed in approximately 10,000 women, and over 3,000 women die from the malignancy. In addition, HPV is implicated as a cause of other cancers involving the genital tract, male and female, and the head and neck. ^ Gardasil, a vaccine against HPV, was licensed by the FDA in June 2006. Early study results have shown Gardasil to be safe and effective at preventing HPV infections that are commonly associated with the development of cervical cancer, as well as other HPV-related cancers and genital warts. The vaccine is most effective when administered in childhood, before initial exposure to HPV, which typically occurs shortly after the onset of sexual activity. Accordingly, the CDC's Advisory Committee on Immunization Practices (ACIP) has recommended routine vaccination of females aged 11-12 years. ^ Taking the ACIP recommendation one step further, many states have considered school-based mandates of the HPV vaccine in an attempt to reduce the burden of HPV-related illness, in particular to reduce the disparately high incidence of cervical cancer in medically underserved populations. These mandate attempts have sparked heated debate—highlighting public concerns regarding adolescent sexuality, corporate greed, and vaccines in general. ^ Methods. My research focuses on publicly available sources of information such as medical journals, government reports (federal and state), NGO reports, newspapers, and books. I begin with a background discussion of HPV, cervical cancer, and the HPV vaccine. I then discuss public health policy issues related to vaccines, vaccine mandates, and HPV-related illness. Specifically, I discuss the public health benefit of previous vaccine mandates, the legality of vaccine mandates, and the undue corporate influence on the politics of instituting HPV vaccine mandates. In addition, I examine some of the causes behind the anti-vaccine movement and the controversy surrounding adolescent sexuality as it pertains to the HPV vaccine. In the final section, I focus on the recent failed attempt by Governor Rick Perry to mandate the HPV vaccine in Texas. A retrospective analysis of Governor Perry's policy decisions is undertaken and recommendations are made regarding future attempts to mandate the HPV vaccine, or other vaccines under development for similar sexually transmitted viral diseases such as HIV and herpes simplex. ^ Results. In Texas, as in other states across the country, HPV vaccine mandates faced opposition from those who, while they may support mandates of other vaccines, oppose mandates for the HPV vaccine based largely on the idea that HPV is a sexually transmitted disease—they see responsible sexual behavior as the appropriate method for preventing HPV-related illness. A second major group of opposition comes from those who are generally opposed to all vaccine mandates, due to concerns that mandates are intended primarily for the financial benefit of the pharmaceutical industry or due to concerns—largely unfounded—that vaccines pose a greater health threat than the illnesses they are designed to prevent. ^ Conclusion. In order to reduce opposition to vaccine mandates, care must be taken to educate the public regarding the benefits of vaccination by mobilizing the public health sector, avoid the impression that the decision to institute mandates is rash or pressured by allowing time for open debate, and minimize lobbying efforts by vaccine manufacturers. ^

Parental acculturation and adolescent HPV uptake among Hispanics: Results from the California Health Interview Survey

Background. The Centers for Disease Control and Prevention (CDC), the American Cancer Society (ACS), and the American College of Obstetricians and Gynecologists (ACOG) all recommend the HPV vaccine for girls 11-12. The vaccine has the potential to reduce cervical cancer disparities if it is used by populations that do not participate in screening. Evidence suggests that incidence and mortality are higher among Hispanic women compared to non-Hispanic white women because they do not participate in screening. Past literature has found that acculturation has a mixed effect on cervical cancer screening and immunization. Little is known about whether parental acculturation is associated with adolescent HPV vaccine uptake among Hispanics and the mechanisms through which acculturation may affect vaccine uptake.^ Aims. To examine the association between parental acculturation and adolescent HPV uptake among Hispanics in California and test the structural hypothesis of acculturation by determining if socioeconomic status (SES) and health care access mediate the association between acculturation and HPV vaccine uptake.^ Methods. Cross-sectional data from the 2007 California Health Interview Survey (CHIS) were used for bivariate and multivariate logistic regression analyses. The sample used for analysis included 1,090 Hispanic parents, with a daughter age 11-17, who answered questions about the HPV vaccine. Outcome variable of interest was HPV vaccine uptake (≥1dose). Independent variables of interest were language spoken at home (a proxy variable for acculturation), household income (percent of federal poverty level), education level, and health care access (combined measure of health insurance coverage and usual source of care).^ Results. Parents who spoke only English or English and Spanish in the home were more likely to get the HPV vaccine for their daughter than parents who only spoke Spanish (Odds Ratio [OR]: 0.55, 95% Confidence Interval [CI]: 0.31-0.98). When SES and health care access variables were added to the logistic regression model, the association between language acculturation and HPV vaccine uptake became non-significant (OR: 0.68, 95% CI: 0.35-1.29). Both income and health care access were associated with uptake. Parents with lower income or who did not have insurance and a usual source of care were less likely to have a vaccinated daughter.^ Discussion. Socioeconomic status and health care access have a more proximal effect on HPV vaccine uptake than parental language acculturation among Hispanics in California.^ Conclusion. This study found support for the structural hypothesis of acculturation and suggest that interventions focus on informing low SES parents who lack access to health care about programs that provide free HPV vaccines.^

Impact of maternal Tdap vaccination on pertussis infection in young infants

Undiagnosed infected mothers often are the source of pertussis illness in young infants. The Centers for Disease Control and Prevention (CDC) recommends Tdap vaccine for post-partum women before hospital discharge. This intervention has been implemented at Ben Taub General Hospital (BTGH) in Houston, TX since January 2008. Our objective was to compare the proportion of infants born at BTGH and developing pertussis to the total number of pertussis cases before and after the intervention. Methods. We conducted a cross-sectional comparative study between the pre-intervention (7/2000 to 12/2007) and post-intervention (1/2008 to 5/2009) periods. Information on pertussis diagnosis was determined using ICD-9 codes, infection control records, and molecular microbiology reports from Texas Children's Hospital (TCH) and BTGH. Only patients ≤ 6 months of age with laboratory-confirmed B. pertussis infection were included in the study. Results. 481 infants had pertussis illness; 353 (73.3%) during pre-intervention and 128 (26.6%) during post-intervention years. The groups were comparable in all measures including age (median 73 vs. 62.5 days; p=0.08), gender (males 54.2%; p=0.47), length of hospitalization (median 9.8 vs. 4 9.5 days; p=0.5), outcomes (2 deaths in each period; p=0.28) and pertussis illness at TCH (95.2% vs. 95.3%; p=0.9). The proportion of pertussis patients born at BTGH, and thus amenable to protection by the intervention, was not statically different between the two periods after adjusting for age, gender and ethnicity (7.3% vs. 9.3%; an OR=1.05, 95% CI 0.5-2.1, p=0.88). Conclusions. Vaccinating only mothers with Tdap in the post-partum period does not reduce the proportion of pertussis in infants age ≤ 6 months. Efforts should be directed at Tdap immunization of not only mothers, but also all household and key contacts of newborns to protect them against pertussis illness before the primary DTaP series is completed.^