Transcriptional signature of durable effector T cells elicited by a replication defective HCMV vaccine.

Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive "transient" and "durable" expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination.

Immunogenicity of 2 or 3 Doses of 9vHPV Vaccine in U.S. Female Individuals 15 to 26 Years of Age.

Immunogenicity of Two or Three Doses of 9vHPV VaccineThis noninferiority trial examined two versus three doses of 9-valent human papillomavirus (9vHPV) vaccine in individuals 15 to 26 years of age in the United States. In an unplanned interim analysis of female participants, two doses of 9vHPV vaccine appeared to elicit similar rates of seroconversion and antibody titers for each of the nine HPV genotypes to three doses at 1 month postvaccination.

Safety and Immunogenicity of a Delayed Heterologous Avian Influenza A(H7N9) Vaccine Boost Following Different Priming Regimens: A Randomized Clinical Trial.

BACKGROUND: Influenza A (H7N9) has caused multiple disease waves with evidence of strain diversification. Optimal influenza A (H7N9) prime-boost vaccine strategies are unknown. METHODS: We recruited participants who had received monovalent inactivated A/Shanghai/2/2013 (H7N9) vaccine (MIV) approximately 5 years earlier, as follows: MIV with MF59 (MF59 × 2 group), MIV with AS03 (AS03 × 2 group), unadjuvanted MIV (No Adj group), MIV with MF59 or AS03 followed by unadjuvanted MIV (Adjx1 group), and A/H7-naive (unprimed group). Participants were randomized to receive 1 dose of AS03-adjuvanted or unadjuvanted A/Hong Kong/125/2017 (H7N9) MIV and were followed for safety and immunogenicity using hemagglutination inhibition (HAI) and neutralizing antibody assays. RESULTS: We enrolled 304 participants: 153 received the adjuvanted boost and 151 received the unadjuvanted boost. At 21 days postvaccination, the proportion of participants with HAI antibody titers against the boosting vaccine strain of ≥40 in the adjuvanted and unadjuvanted arms, respectively, were 88% and 49% in MF59 × 2 group, 89% and 75% in AS03 × 2 group, 59% and 20% in No Adj group, 94% and 55% in Adjx1group, and 9% and 11% in unprimed group. CONCLUSIONS: Serologic responses to a heterologous A(H7N9) MIV boost were highest in participants primed and boosted with adjuvant-containing regimens. CLINICAL TRIALS REGISTRATION: NCT03738241.

Immunogenicity of NVX-CoV2373 heterologous boost against SARS-CoV-2 variants.

As part of a multicenter study evaluating homologous and heterologous COVID-19 booster vaccines, we assessed the magnitude, breadth, and short-term durability of binding and pseudovirus-neutralizing antibody (PsVNA) responses following a single booster dose of NVX-CoV2373 in adults primed with either Ad26.COV2.S, mRNA-1273, or BNT162b2 vaccines. NVX-CoV2373 as a heterologous booster was immunogenic and associated with no safety concerns through Day 91. Fold-rises in PsVNA titers from baseline (Day 1) to Day 29 were highest for prototypic D614G variant and lowest for more recent Omicron sub-lineages BQ.1.1 and XBB.1. Peak humoral responses against all SARS-CoV-2 variants were lower in those primed with Ad26.COV2.S than with mRNA vaccines. Prior SARS CoV-2 infection was associated with substantially higher baseline PsVNA titers, which remained elevated relative to previously uninfected participants through Day 91. These data support the use of heterologous protein-based booster vaccines as an acceptable alternative to mRNA or adenoviral-based COVID-19 booster vaccines. This trial was conducted under ClinicalTrials.gov: NCT04889209.

Disseminated vaccine-induced varicella infection in a kidney transplant recipient.

A 33-year-old kidney transplant (KT) recipient presented with a disseminated pruritic, painful, vesicular rash and hepatitis 3 weeks after receiving a varicella vaccine (VAR). A skin lesion biopsy sent to the Centers for Disease Control and Prevention for genotyping confirmed vaccine-strain varicella-zoster virus (VZV) (Oka strain; vOka). The patient was successfully treated with intravenous acyclovir during a prolonged hospital stay. This case supports the contraindication of VAR in adult KT recipients and highlights the potential for severe illness when used in this population. Optimally, VZV-seronegative KT candidates should receive VAR before starting immunosuppressive medications. If this opportunity is missed, the recombinant varicella-zoster vaccine might be considered following transplantation as it is already recommended to prevent herpes zoster in VZV-seropositive immunocompromised adults. Further study is needed as data are limited on the safety and efficacy of recombinant varicella-zoster vaccine for primary varicella prevention in VZV-seronegative immunocompromised adults.

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exhibits reduced susceptibility to vaccine-induced neutralizing antibodies, requiring a boost to generate protective immunity. We assess the magnitude and short-term durability of neutralizing antibodies after homologous and heterologous boosting with mRNA and Ad26.COV2.S vaccines. All prime-boost combinations substantially increase the neutralization titers to Omicron, although the boosted titers decline rapidly within 2 months from the peak response compared with boosted titers against the prototypic D614G variant. Boosted Omicron neutralization titers are substantially higher for homologous mRNA vaccine boosting, and for heterologous mRNA and Ad26.COV2.S vaccine boosting, compared with homologous Ad26.COV2.S boosting. Homologous mRNA vaccine boosting generates nearly equivalent neutralizing activity against Omicron sublineages BA.1, BA.2, and BA.3 but modestly reduced neutralizing activity against BA.2.12.1 and BA.4/BA.5 compared with BA.1. These results have implications for boosting requirements to protect against Omicron and future variants of SARS-CoV-2. This trial was conducted under ClincalTrials.gov: NCT04889209.

A phase I randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability, and immunogenicity of a live-attenuated quadrivalent dengue vaccine in flavivirus-naïve and flavivirus-experienced healthy adults.

Dengue (DENV) is a mosquito-borne virus with four serotypes causing substantial morbidity in tropical and subtropical areas worldwide. V181 is an investigational, live, attenuated, quadrivalent dengue vaccine. In this phase 1 double-blind, placebo-controlled study, the safety, tolerability, and immunogenicity of V181 in baseline flavivirus-naïve (BFN) and flavivirus-experienced (BFE) healthy adults were evaluated in two formulations: TV003 and TV005. TV005 contains a 10-fold higher DENV2 level than TV003. Two-hundred adults were randomized 2:2:1 to receive TV003, TV005, or placebo on Days 1 and 180. Immunogenicity against the 4 DENV serotypes was measured using a Virus Reduction Neutralization Test (VRNT60) after each vaccination and out to 1 year after the second dose. There were no discontinuations due to adverse events (AE) or serious vaccine-related AEs in the study. Most common AEs after TV003 or TV005 were headache, rash, fatigue, and myalgia. Tri- or tetravalent vaccine-viremia was detected in 63.9% and 25.6% of BFN TV003 and TV005 participants, respectively, post-dose 1 (PD1). Tri- or tetravalent dengue VRNT60 seropositivity was demonstrated in 92.6% of BFN TV003, 74.2% of BFN TV005, and 100% of BFE TV003 and TV005 participants PD1. Increases in VRNT60 GMTs were observed after the first vaccination with TV003 and TV005 in both flavivirus subgroups for all dengue serotypes, and minimal increases were measured PD2. GMTs in the TV003 and TV005 BFE and BFN groups remained above the respective baselines and placebo through 1-year PD2. These data support further development of V181 as a single-dose vaccine for the prevention of dengue disease.

Human papillomavirus dose reminder preferences among parents from a diverse clinical sample: a qualitative study.

Reminders are an important method for encouraging patients to return for follow-up visits, such as for successive doses of the human papillomavirus (HPV) vaccine. However, patients may have preferences for different types of reminders. This study examined which reminder methods parents of pediatric patients found most useful and their thoughts on how the reminders helped them to complete their children's HPV vaccine series. This qualitative study was conducted on a purposively sampled group of parents who participated in a multi-level intervention intended to improve uptake and completion of the HPV vaccine series. Parents who agreed to participate were interviewed by phone using semi-structured interviews about their satisfaction with different program components, including reminders they received. Interviews were conducted between May 26, 2016 and October 18, 2017. Thematic analyses of data were conducted using NVivo software. Among 269 program participants invited to participate in the interviews, 157 agreed (58.4%) and 89 were successfully interviewed (33.1%). Participants thought that reminders were effective at helping them return for follow-up visits to ensure their children received all recommended HPV vaccine doses. Although most parents preferred texts, many also favored other reminder methods by themselves or in combination with texts. Parents suggested that the reminders indicate the purpose of the appointment and for which child. Reminders are an important part of a multi-component intervention that aims to increase completion of the HPV vaccine series. Program enrollees prefer different types of reminders, so offering several options may improve returns for follow-up doses.

Homologous and Heterologous Covid-19 Booster Vaccinations.

BACKGROUND: Although the three vaccines against coronavirus disease 2019 (Covid-19) that have received emergency use authorization in the United States are highly effective, breakthrough infections are occurring. Data are needed on the serial use of homologous boosters (same as the primary vaccine) and heterologous boosters (different from the primary vaccine) in fully vaccinated recipients. METHODS: In this phase 1-2, open-label clinical trial conducted at 10 sites in the United States, adults who had completed a Covid-19 vaccine regimen at least 12 weeks earlier and had no reported history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection received a booster injection with one of three vaccines: mRNA-1273 (Moderna) at a dose of 100 µg, Ad26.COV2.S (Johnson & Johnson-Janssen) at a dose of 5×1010 virus particles, or BNT162b2 (Pfizer-BioNTech) at a dose of 30 µg. The primary end points were safety, reactogenicity, and humoral immunogenicity on trial days 15 and 29. RESULTS: Of the 458 participants who were enrolled in the trial, 154 received mRNA-1273, 150 received Ad26.COV2.S, and 153 received BNT162b2 as booster vaccines; 1 participant did not receive the assigned vaccine. Reactogenicity was similar to that reported for the primary series. More than half the recipients reported having injection-site pain, malaise, headache, or myalgia. For all combinations, antibody neutralizing titers against a SARS-CoV-2 D614G pseudovirus increased by a factor of 4 to 73, and binding titers increased by a factor of 5 to 55. Homologous boosters increased neutralizing antibody titers by a factor of 4 to 20, whereas heterologous boosters increased titers by a factor of 6 to 73. Spike-specific T-cell responses increased in all but the homologous Ad26.COV2.S-boosted subgroup. CD8+ T-cell levels were more durable in the Ad26.COV2.S-primed recipients, and heterologous boosting with the Ad26.COV2.S vaccine substantially increased spike-specific CD8+ T cells in the mRNA vaccine recipients. CONCLUSIONS: Homologous and heterologous booster vaccines had an acceptable safety profile and were immunogenic in adults who had completed a primary Covid-19 vaccine regimen at least 12 weeks earlier. (Funded by the National Institute of Allergy and Infectious Diseases; DMID 21-0012 ClinicalTrials.gov number, NCT04889209.).

Heterologous SARS-CoV-2 Booster Vaccinations - Preliminary Report.

Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-µg, Janssen Ad26.COV2.S 5×1010 virus particles, or Pfizer-BioNTech BNT162b2 30-µg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 153 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

A conditionally replication-defective cytomegalovirus vaccine elicits potent and diverse functional monoclonal antibodies in a phase I clinical trial.

A conditionally replication-defective human cytomegalovirus (HCMV) vaccine, V160, was shown to be safe and immunogenic in a two-part, double-blind, randomized, placebo-controlled phase I clinical trial (NCT01986010). However, the specificities and functional properties of V160-elicited antibodies remain undefined. Here, we characterized 272 monoclonal antibodies (mAbs) isolated from single memory B cells of six V160-vaccinated subjects. The mAbs bind to diverse HCMV antigens, including multiple components of the pentamer, gB, and tegument proteins. The most-potent neutralizing antibodies target the pentamer-UL subunits. The binding sites of the antibodies overlap with those of antibodies responding to natural HCMV infection. The majority of the neutralizing antibodies target the gHgL subunit. The non-neutralizing antibodies predominantly target the gB and pp65 proteins. Sequence analysis indicated that V160 induced a class of gHgL antibodies expressing the HV1-18/KV1-5 germline genes in multiple subjects. This study provides valuable insights into primary targets for anti-HCMV antibodies induced by V160 vaccination.

Functional Evaluation and Genetic Evolution of Human T-Cell Responses After Vaccination With a Conditionally Replication-Defective Cytomegalovirus Vaccine.

BACKGROUND: Cytomegalovirus (CMV) can cause congenital infection and is the leading cause of nongenetic newborn disabilities. V160, a conditionally replication-defective virus, is an investigational vaccine under evaluation for prevention of congenital CMV. The vaccine was well tolerated and induced both humoral and cellular immunity in CMV-seronegative trial participants. T-cell-mediated immunity is important for immune control of CMV. Here we describe efforts to understand the quality attributes of the T-cell responses induced by vaccination. METHODS: Using multicolor flow cytometry, we analyzed vaccine-induced T cells for memory phenotype, antigen specificity, cytokine profiles, and cytolytic potential. Moreover, antigen-specific T cells were sorted from 4 participants, and next-generation sequencing was used to trace clonal lineage development during the course of vaccination using T-cell receptor ß-chain sequences as identifiers. RESULTS: The results demonstrated that vaccination elicited polyfunctional CD4 and CD8 T cells to 2 dominant antigens, pp65 and IE1, with a predominantly effector phenotype. Analysis of T-cell receptor repertoires showed polyclonal expansion of pp65- and IE1-specific T cells after vaccination. CONCLUSION: V160 induced a genetically diverse and polyfunctional T-cell response and the data support further clinical development of V160 for prevention of CMV infection and congenital transmission. CLINICAL TRIALS REGISTRATION: NCT01986010.

Quantitative and qualitative assessment of an all-inclusive postpartum human papillomavirus vaccination program.

BACKGROUND: A postpartum human papillomavirus vaccination program was locally implemented to address low initiation rates among young adults. Within 20 months, the program achieved high vaccine initiation and series completion rates. Based on the program's success, it was expanded to all 36 counties served by a public hospital. OBJECTIVE: This study aimed to conduct a quantitative and qualitative evaluation to examine the success and limitations of the program when expanded from 1 county to 36 counties, many of which are home to rural and medically underserved communities. STUDY DESIGN: Patient navigators reviewed the electronic medical records and immunization registry records of women aged ≤26 years, who delivered an infant at the public hospital, to determine whether they needed to initiate or complete the human papillomavirus vaccine series. Eligible women were counseled and offered the human papillomavirus vaccine during their hospital stay. Patient navigators scheduled follow-up injections in addition to the mother's postpartum or her infant's well-child visits, made reminder phone calls, and rescheduled missed appointments. Descriptive statistics, including frequencies and proportions, were used for patients approached in the initial and expansion programs. Frequencies from the initial and expansion programs were examined separately. Qualitative interviews were conducted with the clinic staff to evaluate the program. The qualitative analyses were conducted using NVivo (QSR International, Melbourne, Australia, version 10). RESULTS: Both initial and expanded programs achieved vaccine completion rates above 70%. Of the 2631 eligible postpartum women enrolled in the initial program, 785 (30%) had already been fully vaccinated. Of the remaining 1846 women, 1265 (69%) women received their first dose, and 196 (11%) women received their second or third dose on the postpartum unit. Of the 1461 women who received at least 1 dose through the initial program, 1124 (77%) completed all 3 doses. Of the 4330 eligible postpartum women enrolled in the expanded program, 886 (21%) had already been fully vaccinated. Of the remaining 3444 women, 2284 (66%) received their first dose, and 343 (10%) received their second or third dose on the postpartum unit. Of the 2627 women receiving at least 1 dose through the expanded program, 1932 (74%) completed all 3 doses. Clinic staff interviewed felt the program benefited the postpartum unit and clinics, because it increased patient knowledge of the vaccine, increased patient volume for vaccination, and gave healthcare providers more time to focus on other tasks. CONCLUSION: Human papillomavirus vaccination on the postpartum unit is an effective way to increase catchup rates and is well accepted by healthcare providers. High completion rates can be achieved if adequate support is provided, even among patients residing in rural or underserved areas who need extensive support to access primary healthcare services. Although this particular program may be considered costly, it is overall effective because the vaccine prevents 5 different types of cancer in women. The inclusion of human papillomavirus vaccination in routine postpartum care is a relatively easy way to reach many adults not vaccinated at a younger age and could help address low vaccination rates among young women in the United States, including hard-to-reach populations.

Use of patient navigators to increase HPV vaccination rates in a pediatric clinical population.

A patient navigator (PN) program was implemented in pediatric clinics to increase uptake of the human papillomavirus (HPV) vaccine. The purpose of this study is to examine the impact of this program. All visits between April 1, 2013 and December 31, 2017 for 9-17 year old patients at 3 program and 5 non-program clinics were examined using electronic medical records. These dates included patient visits before and after program initiation (February 1, 2015). Visits including 1 dose of the HPV vaccine were assessed as a proportion of total visits for each month. Multivariable binary logistic regression was used to examine the odds of HPV vaccination across time, between program and non-program clinics, and age group. A total of 128,051 visits by 21,395 patients were examined. HPV vaccines were administered during 12,742 visits (10.0%). Odds of HPV vaccination during visits by 13-17 year olds was greater than during visits by 9-12 year olds in the pre-intervention period (odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.04-1.19). However, this association changed during the intervention period, with odds of HPV vaccination among visits by 13-17 year olds lower compared to visits by 9-12 year olds (OR: 0.78, 95% CI: 0.75-0.82). The odds of HPV vaccination were elevated among 9-12 year olds in program clinics as compared to 2014, the year before the program was implemented. Having on-site PNs can increase the frequency of HPV vaccination in pediatric clinics, particularly among patients 9-12 years of age.

An educational intervention to improve attitudes regarding HPV vaccination and comfort with counseling among US medical students.

Many medical students are not comfortable recommending the human papillomavirus (HPV) vaccine because they do not feel prepared to discuss it with their patients. A prior study demonstrated that this is particularly a problem among unvaccinated students. Our purpose was to determine if medical student attitudes and comfort with counseling could be improved by attending a single lecture delivered by an expert on the topic. To assess the effects of the educational program, we conducted pre- and posttests on medical students before and after a single lecture on HPV vaccination. Changes in items related to attitude and comfort were examined. Student characteristics associated with changes in scores were also examined and compared. A total of 256 medical students participated in the pre- and posttests. Before the lecture, students demonstrated low knowledge of HPV vaccination and did not feel comfortable counseling parents of younger patients. However, students <30 years of age demonstrated significant improvements after the lecture in comfort. Asian and Hispanic students showed the greatest improvement in comfort with counseling, as did students who reported they had not received the HPV vaccine. Attending a single lecture given by an expert can improve medical students' attitudes and comfort with HPV vaccine counseling, especially if the students were not vaccinated themselves. This study suggests that including material on HPV vaccination in the standard medical student curriculum could help increase physician recommendation for the HPV vaccine.

A Replication-Defective Human Cytomegalovirus Vaccine Elicits Humoral Immune Responses Analogous to Those with Natural Infection.

Human cytomegalovirus (HCMV) can cause congenital infections, which are a leading cause of childhood disabilities. Since the rate of maternal-fetal transmission is much lower in naturally infected (HCMV-seropositive) women, we hypothesize that a vaccine candidate capable of eliciting immune responses analogous to those of HCMV-seropositive subjects may confer protection against congenital HCMV. We have previously described a replication-defective virus vaccine based on strain AD169 (D. Wang, D. C. Freed, X. He, F. Li, et al., Sci Transl Med 8:362ra145, 2016, https://doi.org/10.1126/scitranslmed.aaf9387). The vaccine, named V160, has been shown to be safe and immunogenic in HCMV-seronegative human subjects, eliciting both humoral and cellular immune responses (S. P. Adler, S. E. Starr, S. A. Plotkin, S. H. Hempfling, et al., J Infect Dis 220:411-419, 2019, https://doi.org/10.1093/infdis/171.1.26). Here, we further showed that sera from V160-immunized HCMV-seronegative subjects have attributes similar in quality to those from seropositive subjects, including high-avidity antibodies to viral antigens, coverage against a panel of genetically distinct clinical isolates, and protection against viral infection in diverse types of human cells in culture. More importantly, vaccination appeared efficient in priming the human immune system, inducing memory B cells in six V160 recipients at frequencies comparable to those of three HCMV-seropositive subjects. Our results demonstrate the ability of V160 to induce robust and durable humoral memory responses to HCMV, justifying further clinical evaluation of the vaccine against congenital HCMV.IMPORTANCEIn utero HCMV infection can lead to miscarriage or childhood disabilities, and an effective vaccine is urgently needed. Since children born to women who are seropositive prior to pregnancy are less likely to be affected by congenital HCMV infection, it has been hypothesized that a vaccine capable of inducing an immune response resembling the responses in HCMV-seropositive women may be effective. We previously described a replication-defective virus vaccine that has been demonstrated safe and immunogenic in HCMV-seronegative subjects. Here, we conducted additional analyses to show that the vaccine can induce antibodies with functional attributes similar to those from HCMV-seropositive subjects. Importantly, vaccination can induce long-lived memory B cells at frequencies comparable to those seen in HCMV-seropositive subjects. We conclude that this vaccine is a promising candidate that warrants further clinical evaluation for prevention of congenital HCMV.

Regional variations in human papillomavirus prevalence across time in NHANES (2003-2014).

INTRODUCTION: The consequences of low human papillomavirus (HPV) vaccination in Census regions with higher incidence of cervical cancer may contribute to continued disparities. Our purpose was to evaluate regional variations in HPV prevalence across time. METHODS: Repeated cross-sectional data from the National Health and Nutrition Examination Survey (NHANES), 2003-2014 were examined. Participants included females 14 to 34 years old who provided adequate vaginal samples for HPV DNA typing (N = 6387). Region of residence and HPV vaccination status associations with HPV prevalence were examined using chi-square and multivariable logistic regression. HPV types were grouped according to vaccine-type HPV (types 6, 11, 16, 18) and risk (high or low-risk). Time and vaccination status were included in subsequent models for post-licensure survey cycles (2007-2014) to assess their effects on observed associations. RESULTS: No decreases in vaccine-type HPV prevalence were found between the prevaccine cycles (2003-2006) and early post-licensure cycles (2007-2010, p > 0.05). Vaccine-type HPV prevalence decreased in late post-licensure years (2011-2014) compared to prevaccine years (2003-2006, p = 0.001). The highest prevalence of vaccine-type HPV occurred in the South (8.6%) and Midwest (8.6%), followed by the West (4.8%), and the Northeast (3.5%) in late post-licensure years. Lower odds of vaccine-type HPV across time in post-licensure survey cycles were found to be attributable to time, and more strongly to HPV vaccination. CONCLUSIONS: There were regional variations in vaccine-type HPV prevalence between prevaccine and post-licensure years. These decreases appeared to be at least partially attributable to HPV vaccination. Programs are needed to address geographical disparities in HPV vaccination.

Caregiver acceptance of a patient navigation program to increase human papillomavirus vaccination in pediatric clinics: a qualitative program evaluation.

Objective: The purpose of this evaluation was to examine the acceptability of a multi-component patient navigator (PN) intervention program designed to decrease barriers to human papillomavirus (HPV) vaccination among caregivers of adolescents. We sought to understand the most important components of the program from the caregivers' perspective and to evaluate remaining barriers to vaccination. Method: Caregivers of children 9-17 years old (N = 102) participated in qualitative semi-structured interviews with questions informed by the Theory of Planned Behavior. These interviews assessed experiences with a PN program which offered HPV vaccination, scheduling, and reminders in pediatric clinics. We included randomly selected 46 program participant transcripts and 11 decliner transcripts. A thematic approach was used to analyze transcripts for themes related to acceptability of HPV vaccination, important program components, and any problems encountered. Results: Major themes included: reasons for making HPV vaccination decision, helpful program components and suggestions for improvement, and remaining barriers to vaccination. Those who declined vaccination stated that their child was too young or not ready to think about sex, or they did not have enough information to make a decision. However, they felt that PNs were respectful of their decision. Program participants felt that vaccination was an important way to prevent cancer. Program participants had often not been aware of the vaccine and felt that having it explained was very helpful. Conclusion: This program evaluation found that caregivers of pediatric patients, even those who declined the HPV vaccine, appreciated the program and felt it provided important information about the vaccine.