23-valent Vaccine Research Articles

Partnerships in the introduction of new routine vaccines in Bangladesh: evidence from a prospective process evaluation

ObjectiveTo assess the contribution of partners in the introduction of two new vaccines concurrently: pneumococcal 10-valent conjugate vaccine (PCV-10) and inactivated polio vaccine (IPV) into the routine Expanded Programme on...

Immunogenicity and safety of quadrivalent and 9-valent human papillomavirus vaccines in Indian clinical trial participants

ABSTRACT The quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) and 9-valent HPV (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccines have demonstrated efficacy, immunogenicity, and safety in international clinical trials. We report outcomes from three completed clinical trials in India: a single-arm study (V501–029 [NCT00380367]) in Indian girls (aged 9–15 years; N = 110) evaluating qHPV vaccine immunogenicity and safety; a subgroup analysis (n = 225) of Indian girls/boys (9–15 years) and women (16–26 years) from a global study (V503–002 [NCT00943722]) evaluating 9vHPV vaccine immunogenicity and safety; and a qHPV vaccine post-marketing safety surveillance study (V501–125) in Indian females (aged 9–45 years; N = 188) vaccinated during routine care. In V501–029 and V503–002, HPV vaccines were administered as 3 doses (Day 1, Month 2, Month 6). Serum HPV antibodies were evaluated by competitive Luminex immunoassays at Day 1 and Month 7 (both studies) and Months 12, 24, and 36 (V503–002 only). Adverse events (AEs) were collected by Vaccination Report Card. In V501–125, participants were actively surveilled for serious AEs (SAEs) within 30 days post-qHPV vaccination. In per-protocol analyses, qHPV and 9vHPV vaccines induced robust anti-HPV6/11/16/18 (V501–029) and HPV6/11/16/18/31/33/45/52/58 (V503–002) responses, respectively; ≥97% of participants seroconverted at Month 7 for each vaccine HPV type in both studies, and antibody responses persisted through 36 months in V503–002. The most common AEs were injection-site-associated. Most AEs were mild/moderate; no deaths, vaccine-related SAEs, or discontinuations due to AEs were reported. In V501–125, no SAE was reported. Overall, the qHPV and 9vHPV vaccines elicited robust antibody responses and were generally well tolerated in Indian participants.

Development and characterization of anti-HPV16 monoclonal antibodies for assembly of an HPV16 detection kit.

Quality control is very important during the development of 3-valent (16/18/58), 9-valent (6/11/16/18/31/33/45/52/58), and 15-valent human papillomavirus (HPV) vaccines (6/11/16/18/31/33/35/39/45/52/56/58/59/68). All 3-valent, 9-valent, and 15-valent HPV vaccines contain the HPV16 antigen; therefore, a detection method that can specifically identify HPV16 in vaccines is urgently required. This study aimed to develop and characterize monoclonal antibodies to assemble a highly specific HPV16 detection kit. The HPV16 L1 pentameric protein developed as an immunogen was used to prepare monoclonal antibodies. From the pool of prepared monoclonal antibodies, we selected 4G12 and 5A6 to screen and evaluate their subtypes, specificity, neutralizing activity, serum competition, binding affinity, and gene sequencing. After these characterizations, an enzyme-linked immunosorbent assay kit for these monoclonal antibodies was developed, and excellent quality was demonstrated in the assessment of linearity, repeatability, and specificity. The developed detection kit has great potential for wide use in clinical testing and quality control in vaccine production processes.

Spatial and temporal analysis of invasive pneumococcal disease due to erythromycinresistant serotypes

ObjectivesTo study the spatio-temporal distribution of cases of invasive pneumococcal disease (IPD) due to serotypes resistant to erythromycin and its relationship with community consumption of macrolides and childhood vaccination coverage. MethodsWe selected IPD cases in adults over 59 years old, residents in the Community of Madrid (MC), notified in the period 2007–2016. The variables studied were obtained from the Vaccination Information Systems and the Pharmaceutical Service. The cut-off point (minimum inhibitory erythromycin concentration > 0.5 mg/L) of the EUCAST classification was used to define erythromycin resistant serotypes. We used JointPoint to estimate the incidence trends by erythromycin resistant serotypes included in the 13-valent vaccine (STPCV13) and not included in it (STnoPCV13). The association of these incidences with the community consumption of macrolides and vaccination coverage was made using Poisson models. Statistical scanning was used for the detection of temporal-spaces clusters of cases. Results1936 cases were identified, of which 427 erythromycin resistant serotypes were identified. The incidence of all cases due to resistant serotypes was decreasing (AAPC: −5,40%). During the period studied, the incidence of cases due to erythromycin resistant STPCV13 was decreasing with an annual percentage change (APC): −13.8 and was inversely associated with childhood vaccination coverage (IRR 0.641), while that of cases due to erythromycin resistant STnoPCV13 was ascending (APC): 4.5; and was not associated with coverage. 1 cluster was detected by STnoPCV13 and none by STPCV13 after the date of inclusion of the 13-valent in the childhood vaccination calendar. ConclusionsThe decrease in IPD due to resistant STPCV13 was associated with an increase in childhood vaccination coverage. The presence of clusters due to STnoPCV13 after the date of inclusion of the 13-valent vaccine in the childhood vaccination calendar indicates serotypes replacement. The increase in cases of resistant STnoPCV13 could be related to the replacement of vaccine serotypes in nasopharyngeal colonization, facilitated by the consumption of macrolides still at high levels in MC.

Head-to-head comparison of 7 high-sensitive human papillomavirus nucleic acid detection technologies with the SPF10 LiPA-25 system

BackgroundThe SPF10 LiPA-25 system for human papillomavirus (HPV) detection with high analytical performance is widely used in HPV vaccine clinical trials. To develop and evaluate more valent HPV vaccines, other comparable methods with simpler operations are needed. MethodsThe performance of the LiPA-25 against that of other 7 assays, including 4 systems based on reverse hybridization (Bohui-24, Yaneng-23, Tellgen-27, and Hybribio-16) and 3 real-time polymerase chain reaction (PCR) assays (Hybribio-23, Bioperfectus-21, and Sansure-26), was evaluated in selected 1726 cervical swab and 56 biopsy samples. A total of 15 HPV genotypes (HPV 6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66) were considered for comparison for each HPV type. ResultsAmong the swab samples, compared to LiPA-25, compatible genotypes were observed in 94.1% of samples for Hybribio-23, 92.8% for Yaneng-23, 92.6% for Bioperfectus-21, 92.4% for Hybribio-16, 91.3% for Sansure-26, 89.7% for Bohui-24, and 88.0% for Tellgen-27. The highest overall agreement of the 15 HPV genotypes combined was noted for Hybribio-23 (κ = 0.879, McNemar's test: P = 0.136), followed closely by Hybribio-16 (κ = 0.877, P< 0.001), Yaneng-23 (κ = 0.871, P < 0.001), Bioperfectus-21 (κ = 0.848, P < 0.001), Bohui-24 (κ = 0.847, P < 0.001), Tellgen-27 (κ = 0.831, P < 0.001), and Sansure-26 (κ = 0.826, P < 0.001). Additionally, these systems were also highly consistent with LiPA-25 for biopsy specimens (all, κ > 0.897). ConclusionsThe levels of agreement for the detection of 15 HPV types between other 7 assays and LiPA-25 were all good, and Hybribio-23 was most comparable to LiPA-25. The testing operation of HPV genotyping should also be considered for vaccine and epidemiological studies.

EE427 Cost-Effectiveness Analysis of HPV Vaccination for Adult Women in China: A Combined Model

China has a total population of about 15.5% HPV affected people. HPV vaccination has been proved effective in significantly reducing the incidence of HPV-related diseases as well as economic burden. This study was to evaluate the effectiveness and cost-effectiveness of Chinese adult women (18 years) receiving 2-valent, 4-valent and 9-valent vaccine compared with no vaccination.

Assessing the Health and Economic Outcomes of a 9-Valent HPV Vaccination Program in the United Kingdom.

Background: The United Kingdom (UK) switched from using the 4-valent human papillomavirus (HPV) vaccine (Gardasil®) to the 9-valent vaccine (Gardasil 9®) in 2021.Objective: To estimate and compare the health and economic outcomes of 2 HPV vaccination programs in the UK targeting girls and boys aged 12-13 years from the perspective of the UK National Health Service. The 2 vaccination strategies were (1) universal vaccination 4-valent (UV4V), using the 4-valent HPV vaccine (4vHPV), and (2) universal vaccination 9-valent (UV9V), using the 9-valent HPV vaccine (9vHPV).Methods: A deterministic heterosexual compartmental disease transmission model was used to track health and economic outcomes over a 100-year time horizon. Outcomes were discounted at an annual rate of 3.5% and 1.5%. All costs were adjusted to 2020 British pounds (£). Health outcomes were measured in quality-adjusted life-years (QALYs), and the summary results were presented as incremental cost-effectiveness ratios (£/QALY gained) when comparing UV4V with UV9V.Results: Using the same vaccine coverage for both programs, the total cumulative cases of HPV-related health outcomes tracked over the 100-year horizon indicated that the relative number of cases averted (UV9V vs UV4V) ranged from 4% (anal male cancers and deaths) to 56% (cervical intraepithelial neoplasia [CIN1]). Assuming that 9vHPV cost £15.18 more than 4vHPV (a cost differential based on discounted list prices), the estimated incremental cost-effectiveness ratio was £8600/QALY gained when discounted at 3.5%, and £3300/QALY gained when discounted at 1.5%. The estimated incremental cost-effectiveness ratios from the sensitivity analyses remained <£28000/QALY over a wide range of parameter inputs and demonstrated that disease utilities, discount rate, and vaccine efficacy were the 3 most influential parameters.Discussion: Consistent with other published studies, the results from this study found that the 9vHPV vaccine prevented a substantial number of cases when compared with the 4vHPV vaccine and was highly cost-effective.Conclusions: These results demonstrate that replacing universal 4vHPV with 9vHPV can prevent a substantial additional number of HPV-related cases/deaths (in both women and men) and remain cost-effective over a range of 9vHPV price premiums.

Assessing the Health and Economic Outcomes of a 9-Valent HPV Vaccination Program in the United Kingdom

Background: The United Kingdom (UK) switched from using the 4-valent human papillomavirus (HPV) vaccine (Gardasil®) to the 9-valent vaccine (Gardasil 9®) in 2021. Objective: To estimate and compare the health and economic outcomes of 2 HPV vaccination programs in the UK targeting girls and boys aged 12-13 years from the perspective of the UK National Health Service. The 2 vaccination strategies were (1) universal vaccination 4-valent (UV4V), using the 4-valent HPV vaccine (4vHPV), and (2) universal vaccination 9-valent (UV9V), using the 9-valent HPV vaccine (9vHPV). Methods: A deterministic heterosexual compartmental disease transmission model was used to track health and economic outcomes over a 100-year time horizon. Outcomes were discounted at an annual rate of 3.5% and 1.5%. All costs were adjusted to 2020 British pounds (£). Health outcomes were measured in quality-adjusted life-years (QALYs), and the summary results were presented as incremental cost-effectiveness ratios (£/QALY gained) when comparing UV4V with UV9V. Results: Using the same vaccine coverage for both programs, the total cumulative cases of HPV-related health outcomes tracked over the 100-year horizon indicated that the relative number of cases averted (UV9V vs UV4V) ranged from 4% (anal male cancers and deaths) to 56% (cervical intraepithelial neoplasia [CIN1]). Assuming that 9vHPV cost £15.18 more than 4vHPV (a cost differential based on discounted list prices), the estimated incremental cost-effectiveness ratio was £8600/QALY gained when discounted at 3.5%, and £3300/QALY gained when discounted at 1.5%. The estimated incremental cost-effectiveness ratios from the sensitivity analyses remained &lt;£28000/QALY over a wide range of parameter inputs and demonstrated that disease utilities, discount rate, and vaccine efficacy were the 3 most influential parameters. Discussion: Consistent with other published studies, the results from this study found that the 9vHPV vaccine prevented a substantial number of cases when compared with the 4vHPV vaccine and was highly cost-effective. Conclusions: These results demonstrate that replacing universal 4vHPV with 9vHPV can prevent a substantial additional number of HPV-related cases/deaths (in both women and men) and remain cost-effective over a range of 9vHPV price premiums.

On Imported and Domestic Human Papillomavirus Vaccines: Cognition, Attitude, and Willingness to Pay in Chinese Medical Students.

This study aimed to analyze the cognition, attitude, and willingness to pay (WTP) for imported and domestic human papillomavirus (HPV) vaccines in Chinese medical students.MethodsMedical students in Eastern, Central and Western China were investigated. We used the HPV cognitive list to measure the cognition of participants and implemented contingent valuation method (CVM) to value WTP. Tobit model was used to analyze the factors associated with WTP.ResultsThe participants' average score for the 21 cognitive questions was 13.05 (±5.09). Among the participants, 60.82 and 88.01% reported that they would wish to be vaccinated and support the partners to be vaccinated. In addition, 92.54% (670) of the participants were willing to pay for HPV vaccines, at mean values (in RMB) of 1,689.80 (±926.13), 2,216.61 (±1190.62), and 3,252.43 (±2064.71) for imported bivalent, quadrivalent, and 9-valent vaccines, respectively, and at 910.63 (±647.03), 1,861.69 (±1147.80), and 2,866.96 (±1784.41) for their domestic counterparts, respectively. The increase in cognitive score has a positive effect on the WTP for imported vaccines (P < 0.05).ConclusionsMost of the participants were likewise willing to receive the HPV vaccines. Their perceptions of the HPV vaccines valent and origin may affect their willingness to be vaccinated and pay for the vaccines. Increasing awareness of the HPV vaccines and the inclusion of the HPV vaccines in a Medicare reimbursement policy or immunization program could increase the coverage of the HPV vaccine.

Immunogenicity and Safety of a Novel 13-Valent Pneumococcal Vaccine in Healthy Chinese Infants and Toddlers.

BackgroundTo determine the non-inferiority of the seven common serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) in the 13-valent pneumococcal conjugate vaccine (PCV13) with each serotype conjugated to a tetanus toxoid carrier protein and adsorbed on aluminum phosphate and the superiority of its six additional serotypes (1, 3, 5, 6A, 7F, and 19A) to the serotypes in the PCV7.MethodsParticipants were evenly randomized in a 1:1 ratio into either the PCV13 or PCV7 groups, to receive three doses of the vaccine at the age of 3, 4, and 5 months, respectively, and a booster dose between 12 and 15 months of age. Serotype-specific antibodies were measured using a standardized enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic activity (OPA) microcolony assay method.ResultsA total of 1,040 healthy infants were enrolled. All the seven common serotypes in the PCV13 were non-inferior to those in the PCV7 in terms of the serotype-specific IgG production induced; however, non-inferiority was not shown for serotype 6B after the infant series. The proportion of subjects who reached OPA antibody titers ≥ 1:8 in the PCV13 group was 89.25% or higher. Local reactions and systemic events were mild or moderate in severity and similar between the two groups. No new safety signals were observed.ConclusionThe newly developed PCV13 was immunogenic for all serotypes and had a comparable safety profile to the marketed PCV7.

Immunogenicity and safety of the 9-valent human papillomavirus vaccine in Chinese females 9–45 years of age: A phase 3 open-label study

BackgroundThe 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16–26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9–19 years and 27–45 years with Chinese females aged 20–26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9–19 years. MethodsParticipants aged 9–45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded. ResultsIn total, 1990 participants (690 aged 9–19 years; 650 aged 20–26 years; 650 aged 27–45 years) were enrolled. At 1 month post-Dose 3, >99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9–19-year age group were non-inferior to those in participants aged 20–26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27–45-year age group were non-inferior to those in participants aged 20–26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9–19, 20–26, and 27–45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths. ConclusionAntibody responses induced by 9vHPV vaccination in Chinese females aged 9–19 years and 27–45 years were non-inferior to those in Chinese females aged 20–26 years. The vaccine was generally well tolerated.ClinicalTrials.gov Identifier: NCT03903562.

High Diversity of emm Types and Marked Tetracycline Resistance of Group A Streptococci and Other ß-Hemolytic Streptococci in Gabon, Central Africa.

Group A ß-hemolytic streptococcus (GABHS) is a leading pathogen worldwide and post-streptococcal sequelae is a major cause of morbidity and mortality in resource-limited countries. The M protein (coded by the emm gene) is a key virulence factor and a component of GABHS vaccine candidates. As data on BHS in Central Africa are scarce, antibiotic resistance, emm diversity and potential vaccine coverage were investigated. In a prospective cross-sectional study, 1014 Gabonese were screened for streptococcal throat carriage, tonsillopharyngitis and pyoderma by throat and skin smear tests. All BHS were isolated, species were identified and analysis of antibiotic resistance, emm types and emm clusters was performed. One hundred sixty-five BHS were detected, comprising 76 GABHS, 36 group C ß-hemolytic streptococcus (GCBHS) and 53 group G ß-hemolytic streptococcus (GGBHS) in 140 carrier, 9 tonsillopharyngitis and 16 pyoderma isolates. Eighty percentage of GABHS, 78% of GCBHS and 79% of GGBHS were tetracycline resistant. Forty-six emm types were identified. GABHS emm58, emm65 and emm81 were most prevalent (26%). Emm diversity of GABHS was the highest, GCBHS and GGBHS were less divers. Every second GABHS, every third GCBHS and every tenth GGBHS carrier was colonized with emm types detected in tonsillopharyngitis or pyoderma isolates. Tetracycline resistance and emm type diversity was high among BHS carriers in Gabon with a potential coverage of 58% by the 30-valent GABHS vaccine. A relevant overlap of carrier emm types with emm types found in tonsillopharyngitis and pyoderma characterizes a shared pool of circulating BHS strains.

A global snapshot on the prevalent macrolide-resistant emm types of Group A Streptococcus worldwide, their phenotypes and their resistance marker genotypes during the last two decades: A systematic review.

Watchful epidemiological surveillance of macrolide-resistant Group A Streptococcus (MRGAS) clones is important owing to the evolutionary and epidemiological dynamic of GAS. Meanwhile, data on the global distribution of MRGAS emm types according to macrolide resistance phenotypes and genotypes are scant and need to be updated. For this, the present systematic review analyses a global set of extensively characterized MRGAS isolates from patients of diverse ages and clinical presentations over approximately two decades (2000 to 2020) and recaps the peculiar epidemiological features of the dominant MRGAS clones. Based on the inclusion and exclusion criteria, 53 articles (3593 macrolide-resistant and 15,951 susceptible isolates) distributed over 23 countries were dissected with a predominance of high-income countries over low-income ones. Although macrolide resistance in GAS is highly variable in different countries, its within-GAS distribution seems not to be random. emm pattern E, 13 major emm types (emm12, 4, 28, 77, 75, 11, 22, 92, 58, 60, 94, 63, 114) and 4 emm clusters (A-C4, E1, E6, and E2) were significantly associated with macrolide resistance. emm patterns A-C and D, 14 major emm types (emm89, 3, 6, 2, 44, 82, 87, 118, 5, 49, 81, 59, 227, 78) and 3 well-defined emm clusters (A-C5, E3, and D4) were significantly associated with macrolide susceptibility. Scrutinizing the tendency of each MRGAS emm type to be significantly associated with specific macrolide resistance phenotype or genotype, interesting vignettes are also unveiled. The 30-valent vaccine covers ~95% of MRGAS isolates. The presented data urge the importance of comprehensive nationwide sustained surveillance of MRGAS circulating clones particularly in Low and Middle income countries where sampling bias is high and GAS epidemiology is obfuscated and needs to be demystified.

Serotype distribution and antimicrobial resistance of invasive Streptococcus pneumoniae isolates among Croatian adults during a fifteen-year period (2005-2019)

AimTo assess serotype distribution, antibiotic resistance, and vaccine coverage against Streptococcus pneumoniae causing invasive infections in Croatian adults from 2005 to 2019.MethodsIn this retrospective study, invasive pneumococcal strains were collected through a microbiological laboratory network with country coverage >95%. Capsular typing was performed with the Quellung reaction. In vitro susceptibility testing was carried out according to the European Committee on Antimicrobial Susceptibility Testing guidelines. In macrolide-resistant isolates, the presence of ermB and mefA genes was evaluated.ResultsDuring the fifteen-year study period, 1123 invasive pneumococcal isolates were obtained. The most prevalent serotypes were 3, 14, 19A, 9V, 7F, and 23F, comprising 60% of all invasive pneumococcal isolates. Serotype 3 was the dominant serotype, with the highest prevalence in patients ≥65 years of age. Penicillin susceptibility, increased exposure was 18.6%, mostly associated with serotypes 14 and 19A. Resistance to penicillin was low (<1%). Macrolide resistance was 23%, mostly associated with serotypes 14, 19A, and 19F. The coverage with 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) was 80.2% and 93.6%, respectively.ConclusionsThe incidence of invasive pneumococcal disease in adults is highest in patients ≥65 years of age. Penicillin susceptibility, increased exposure and macrolide resistance were mostly associated with serotypes 14 and 19A. PCV13 and PPV23 provide very high serotype coverage. Future studies should evaluate the effects of the 10-valent vaccine, introduced in the Croatian National Immunization Program in June 2019, on serotype distribution and antibiotic resistance rates.

The epidemiology and outcomes of central nervous system infections in Far North Queensland, tropical Australia; 2000-2019.

The epidemiology of central nervous system (CNS) infections in tropical Australia is incompletely defined. A retrospective study of all individuals in Far North Queensland, tropical Australia, who were diagnosed with a CNS infection between January 1, 2000, and December 31, 2019. The microbiological aetiology of the infection was correlated with patients' demographic characteristics and their clinical course. There were 725 cases of CNS infection during the study period, meningitis (77.4%) was the most common, followed by brain abscess (11.6%), encephalitis (9.9%) and spinal infection (1.1%). Infants (24.3%, p<0.0001) and Aboriginal and Torres Strait Islander Australians (175/666 local residents, 26.3%, p<0.0001) were over-represented in the cohort. A pathogen was identified in 513 cases (70.8%); this was viral in 299 (41.2%), bacterial in 175 (24.1%) and fungal in 35 (4.8%). Cryptococcal meningitis (24 cases) was diagnosed as frequently as pneumococcal meningitis (24 cases). There were only 2 CNS infections with a S. pneumoniae serotype in the 13-valent pneumococcal vaccine after its addition to the National Immunisation schedule in 2011. Tropical pathogens-including Cryptococcus species (9/84, 11%), Mycobacterium tuberculosis (7/84, 8%) and Burkholderia pseudomallei (5/84, 6%)-were among the most common causes of brain abscess. However, arboviral CNS infections were rare, with only one locally acquired case-a dengue infection in 2009-diagnosed in the entire study period. Intensive Care Unit admission was necessary in 14.3%; the overall case fatality rate was 4.4%. Tropical pathogens cause CNS infections as commonly as traditional bacterial pathogens in this region of tropical Australia. However, despite being highlighted in the national consensus guidelines, arboviruses were identified very rarely. Prompt access to sophisticated diagnostic and supportive care in Australia's well-resourced public health system is likely to have contributed to the cohort's low case-fatality rate.

Cervical Precancers and Cancers Attributed to HPV Types by Race and Ethnicity: Implications for Vaccination, Screening, and Management.

Racial and ethnic variations in attribution of cervical precancer and cancer to human papillomavirus (HPV) types may result in different HPV vaccine protection, screening test coverage, and clinical management. Pooling data from 7 US studies, we calculated the proportional attribution of precancers and cancers to HPV types using HPV DNA typing from diagnosis. All statistical tests were 2-sided. For all racial and ethnic groups, most cases of cervical intraepithelial neoplasia grade 3 (CIN3) (84.2%-90.8% of 5526) and squamous cell carcinoma (SCC) (90.4%-93.8% of 1138) were attributed to types targeted by the 9-valent vaccine. A higher proportion of CIN3s were attributed to nonvaccine HPV types among non-Hispanic Black women (15.8%) compared with non-Hispanic Asian or Pacific Islander (9.7%; P = .002), non-Hispanic White (9.2%; P < .001), and Hispanic (11.3%; P = .004) women. The proportion of SCCs attributed to 9-valent types was similar by race and ethnicity (P = .80). A higher proportion of CIN3s were attributed to nonvaccine HPV35 among non-Hispanic Black (9.0%) compared with non-Hispanic Asian or Pacific Islander (2.2%), non-Hispanic White (2.5%), and Hispanic (3.0%; all P < .001) women. Compared with CIN3, the proportion of SCCs attributed to HPV35 among non-Hispanic Black women (3.2%) was lower and closer to other groups (0.3%-2.1%; P = .70). The 9-valent HPV vaccine will prevent nearly all cervical precancers and invasive cancers among major racial and ethnic groups in the United States. Adding HPV35 to vaccines could prevent a small percentage of CIN3s and SCCs, with greater potential impact for CIN3s among Black women. HPV screening tests target high-risk HPV types, including HPV35. Future genotyping triage strategies could consider the importance of HPV35- and other HPV16-related types.

Long-Term Effects of Human Papillomavirus Vaccination in Clinical Trials and Real-World Data: A Systematic Review.

The preventive effect of HPV vaccines against anogenital and oropharyngeal cancers has been proven in both clinical trials and real-world data. We reviewed the published evidence about the long-term efficacy and effectiveness of the HPV vaccine in available papers of clinical trials and real-world data. As far as we searched, the longest period of preventive effect for the bivalent, 4-valent, and 9-valent vaccine were 11 years in the Costa Rica trial, 14 years in the FUTURE II, and 8 years in the LTFU extension study of V503-002 and the Scandinavian study, respectively. The sustained clinical effect during the observation period was longest for the 4-valent vaccine. In real-world data, the longest observation period of the vaccine effectiveness was 12 years in an Australian study for the 4-valent vaccine. On the other hand, the longest period of long-term persistence of HPV vaccine-induced seropositivity was 14 years in FUTURE II for the 4-valent vaccine. For the bivalent vaccine, additional long-term follow-up studies may not have been planned due to the launch of the 4-valent and 9-valent vaccines. In some studies of the 9-valent vaccine, the results have not yet been published because of the short observation period. The additional results are expected in the future. In a national immunization program, most girls and boys are inoculated with HPV vaccine by the time puberty begins; thus, it is important to monitor the vaccine effect at least until the sexually active period in their 20s and 30s.

Prevention of pneumococcal infections in childhood: two decades of progress.

This review highlights progress in combating pediatric pneumococcal disease in the era of pneumococcal conjugate vaccines (PCVs). This review is timely given the development of increased valency PCVs for potential use in children. Countries implementing vaccination programs with PCVs have witnessed dramatic reductions in cases of childhood invasive pneumococcal disease (IPD). In the US, the largest decline of IPD followed the introduction of 7-valent PCV with additional decreases following the switch to 13-valent PCV (PCV13). Despite these gains, IPD still occurs in the US but at much lower rates. Likewise, pneumonia hospitalizations and office visits for otitis media have decreased. Nasopharyngeal colonization with pneumococci has persisted due to replacement by nonvaccine serotypes: colonizing non-PCV13 serotypes have less invasive potential. The PCV era has also been marked by reductions in the proportions of pneumococcus showing nonsusceptibility or resistance to some antimicrobial agents. Furthermore, PCVs have an excellent safety profile. Despite proven safety and efficacy, childhood vaccination programs in some countries do not include PCVs, resulting in the majority of global deaths attributable to pneumococcus. Increased worldwide vaccination of children and the development of higher valency vaccines holds additional promise for further reductions in childhood IPD.

Effect of Maternal Immunization With 10-Valent Pneumococcus Conjugate Vaccine (PCV-10), 23-Valent Pneumococcus Polysaccharide Vaccine, or Placebo on the Immunogenicity of PCV-10 in Human Immunodeficiency Virus-Exposed Uninfected Infants: A Randomized Clinical Trial.

The effect of pneumococcal vaccination of mothers with human immunodeficiency virus (HIV) on infant responses to childhood vaccination has not been studied. We compared the immunogenicity of 10-valent pneumococcus conjugate vaccine (PCV-10) in HIV-exposed uninfected infants born to mothers who received PCV-10, 23-valent pneumococcus polysaccharide vaccine (PPV-23), or placebo during pregnancy. Antibody levels against 7 serotypes were measured at birth, before the first and second doses of PCV-10m and after completion of the 2-dose regimen in 347 infants, including 112 born to mothers who received PPV-23, 112 who received PCV-10, and 119 who received placebo during pregnancy. Seroprotection was defined by antibody levels ≥0.35 µg/mL. At birth and at 8 weeks of life, antibody levels were similar in infants born to PCV-10 or PPV-23 recipients and higher than in those born to placebo recipient. After the last dose of PCV-10, infants in the maternal PCV-10 group had significantly lower antibody levels against 5 serotypes than those in the maternal PPV-23 group and against 3 serotypes than those in the maternal placebo group, and they did not have higher antibody levels against any serotype. The seroprotection rate against 7 serotypes was 50% in infants in the maternal PCV-10 group, compared with 71% in both of the maternal PPV-23 and placebo groups (P < .001). Administration of PCV-10 during pregnancy was associated with decreased antibody responses to PCV-10 and seroprotection rates in infants. Considering that PCV-10 and PPV-23 had similar immunogenicity in pregnant women with HIV and that administration of PPV-23 did not affect the immunogenicity of PCV-10 in infants, PPV-23 in pregnancy may be preferred over PCV-10.

Analysis of the clinical efficacy of vaccination against pneumococcal infection in patients with chronic obstructive pulmonary disease in combination with type 2 diabetes mellitus

The study included patients (n=103) with COPD in combination with type 2 diabetes. Primary endpoints were changes dyspnea mMRC score, FEV1, number of exacerbations of COPD, hospitalizations, and a rate of pneumonia. The prognostic indices BODE, DOSE, ADO were also calculated. 13-valent conjugate pneumococcal vaccine PCV-13 and 23-valent polysaccharide vaccine PPV-23 were used for vaccination. It has been established that when vaccination is included in the management plan for patients with COPD in combination with diabetes, the severity of dyspnea decreases, the lung function stabilize both for short-term and 5-years follow-up. Vaccination with PCV-13 and PPV-23 reduce number of exacerbations, a rate of pneumonia and hospitalizations, but long-term efficacy has been demonstrated only for PCV-13. Vaccination with PCV-13 can improve the quality of life and prognosis for patients with COPD in combination with type 2 diabetes. Vaccination of pneumococcal infection in patients with COPD and type 2 diabetes mellitus can reduce the number of exacerbations, incidence of pneumonia and the number of hospitalizations, improve the prognosis and survival of patients using PCV-13 by maintaining efficacy for 5 years of follow-up.