Last data update: Mar 21, 2025. (Total: 48935 publications since 2009)
Records 1-17 (of 17 Records) |
Query Trace: Carlton J[original query] |
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Factors associated with influenza and COVID-19 vaccination among health workers in Lao PDR, 2023
Patthammavong C , Wodniak N , Phounphenghack K , Tengbriacheu C , Soumphonphakdy B , Phixay V , Vongkhamsao C , Khanthamaly V , Patel JC , Montgomery MP , McCarron M , Davis WW , Carlton J , Bazant ES , Moen AC , Nouanthong P . Vaccine 2025 54 127006 ![]() Understanding vaccine uptake and related factors among health care workers is critical to successful vaccination programs. A cross-sectional survey was conducted in central, provincial, district hospitals and health centers among health workers in Lao People's Democratic Republic (PDR) in November 2023 to assess health workers' experience with influenza and COVID-19 vaccination, vaccination uptake, intended uptake, and intention to recommend both vaccinations to patients in the future. Logistic regression was used to identify factors associated with these practices. Among 1228 surveyed health workers in six provinces, 55 % were nurses, assistant nurses, or midwives; 32 % were doctors or assistant doctors; and 14 % had other occupations. Overall, 77 % of respondents were female, and the median age was 34 years (interquartile range 29-42 years). Current influenza vaccination and receipt of COVID-19 booster doses were 70 % (95 % confidence interval [CI]: 62-78 %) and 90 % (95 % CI: 87-92 %), respectively. If vaccines were available for free in the future, approximately 94 % and 92 % of health workers would receive influenza and COVID-19 vaccination, respectively. Nearly all health workers would recommend influenza (98 %) and COVID-19 (95 %) vaccination to their patients. Health workers who had received influenza vaccination prior to the COVID-19 pandemic were more likely to have received current influenza vaccination (adjusted odds ratio [aOR], 95 % CI: 3.7, 2.8-4.9) and to intend to receive influenza vaccination in the future (aOR 2.7, 95 % CI: 1.1-6.8). Health workers who were vaccinated for influenza in the current season were more likely to receive COVID-19 booster doses and to intend to receive future booster doses (aOR, 95 % CI: 2.2, 1.3-3.7 and 2.5, 1.2-5.1, respectively). Intention to recommend influenza vaccination to patients was associated with the intention to recommend COVID-19 vaccination to patients, and vice versa. High acceptance for influenza and COVID-19 vaccination among health workers can support a successful vaccination program in Lao PDR. |
Seasonal influenza vaccination programs in the Americas: A platform for sustainable life-course immunization and its role for pandemic preparedness and response
Nogareda F , Ghiselli M , Velandia-González M , de Mucio B , Jara J , Couto P , Rodriguez A , Rondy M , Vicari A , Ozturk MH , Goldin S , Vilajeliu A , Leidman E , Patel J , Carlton J , Fowlkes AL , Azziz-Baumgartner E , Salas Peraza D , Ropero AM . Vaccines 2024 12 (12) Background: Vaccination is one of the most effective measures to prevent influenza illness and its complications. Since the 1980s, countries and territories in the Americas have progressively implemented influenza vaccination operations in high-risk priority groups—such as older adults, pregnant persons, persons with comorbidities and health workers. Methods: In this review, we present the history and progress of the seasonal influenza program in the Americas, how the program contributed to the efficient and timely roll-out of the COVID-19 vaccines during the pandemic, and how the program can be used to promote immunization operations across the life span for existing and future vaccines. Results: The influenza A(H1N1)pdm09 pandemic in 2009 and the COVID-19 pandemic in 2020–2023 underscored the importance of having a robust seasonal influenza vaccination program for pandemic preparedness and response. Overall, countries with existing seasonal influenza vaccination programs were better prepared and rolled out the delivery of COVID-19 vaccines more quickly and effectively compared to other countries where the influenza vaccination platform was weak or non-existent. Conclusions: Traditionally, national immunization programs of developing countries have been predominately focused on newborns, children younger than five years and school-aged children while often limiting their investment in effective adult vaccination programs; these programs are typically isolated to high-income countries. Countries in Latin America have been the exception, with strong influenza vaccination programs for adults regardless of national income level. The presence of functional and effective adult influenza vaccination programs can also facilitate the acceptance and uptake of other adult vaccines targeting priority groups at higher risk for severe illness or complications. © 2024 by the authors. |
CDC's COVID-19 international vaccine implementation and evaluation program and lessons from earlier vaccine introductions
Soeters HM , Doshi RH , Fleming M , Adegoke OJ , Ajene U , Aksnes BN , Bennett S , Blau EF , Carlton JG , Clements S , Conklin L , Dahlke M , Duca LM , Feldstein LR , Gidudu JF , Grant G , Hercules M , Igboh LS , Ishizumi A , Jacenko S , Kerr Y , Konne NM , Kulkarni S , Kumar A , Lafond KE , Lam E , Longley AT , McCarron M , Namageyo-Funa A , Ortiz N , Patel JC , Perry RT , Prybylski D , Reddi P , Salman O , Sciarratta CN , Shragai T , Siddula A , Sikare E , Tchoualeu DD , Traicoff D , Tuttle A , Victory KR , Wallace A , Ward K , Wong MKA , Zhou W , Schluter WW , Fitter DL , Mounts A , Bresee JS , Hyde TB . Emerg Infect Dis 2022 28 (13) S208-s216 The US Centers for Disease Control and Prevention (CDC) supports international partners in introducing vaccines, including those against SARS-CoV-2 virus. CDC contributes to the development of global technical tools, guidance, and policy for COVID-19 vaccination and has established its COVID-19 International Vaccine Implementation and Evaluation (CIVIE) program. CIVIE supports ministries of health and their partner organizations in developing or strengthening their national capacities for the planning, implementation, and evaluation of COVID-19 vaccination programs. CIVIE's 7 priority areas for country-specific technical assistance are vaccine policy development, program planning, vaccine confidence and demand, data management and use, workforce development, vaccine safety, and evaluation. We discuss CDC's work on global COVID-19 vaccine implementation, including priorities, challenges, opportunities, and applicable lessons learned from prior experiences with Ebola, influenza, and meningococcal serogroup A conjugate vaccine introductions. |
Nationwide introduction of HPV vaccine in Zimbabwe 2018-2019: experiences with multiple cohort vaccination delivery
Carlton JG , Marembo J , Manangazira P , Rupfutse M , Shearley A , Makwabarara E , Hidle A , Loharikar A . PLoS Glob Public Health 2022 2 (4) e0000101 The World Health Organization (WHO) recommends the human papillomavirus (HPV) vaccine for girls aged 9-14 years for cervical cancer prevention and encourages vaccinating multiple cohorts in the first year to maximize impact. The HPV vaccine was introduced nationwide in Zimbabwe in 2018 through a 1-week school-based campaign to multiple cohorts (all girls 10-14 years old), followed by a single cohort (grade 5 girls in school and age 10 girls out-of-school) in 2019. During the 2019 campaign, the multiple cohort's second dose was concurrently delivered with the single cohort's first dose. We interviewed national-level key informants, reviewed written materials, and observed vaccination sessions to document HPV vaccine introduction in Zimbabwe and identify best practices and challenges. Key informants included focal persons from government health and education ministries, in-country immunization partners, and HPV Vaccine Strategic Advisory Group members. We conducted a desk review of policy/strategy documents, introduction plans, readiness reports, presentations, and implementation tools. Vaccination sessions were observed in three provinces during the 2019 campaign. Key informants (n = 8) identified high cervical cancer burden, political will, vaccine availability, donor financing, and a successful pilot program as factors driving the decision to introduce the HPV vaccine nationally. The school-based delivery strategy was well accepted, with strong collaboration between health and education sectors and high community demand for vaccine identified as key contributors to this success. Challenges with transitioning from a multiple age-based to single grade- and age-based target population as well as funding shortages for operational costs were reported. Zimbabwe's first multiple cohort, school-based HPV vaccination campaign was considered successful-primarily due to strong collaboration between health and education sectors and political commitment; however, challenges vaccinating overlapping cohorts in the 2019 campaign were observed. Integration with existing health and vaccination activities and continued resource mobilization will ensure sustainability of Zimbabwe's HPV vaccination program in the future. |
Single-dose versus 7-day-dose metronidazole for the treatment of trichomoniasis in women: an open-label, randomised controlled trial
Kissinger P , Muzny CA , Mena LA , Lillis RA , Schwebke JR , Beauchamps L , Taylor SN , Schmidt N , Myers L , Augostini P , Secor WE , Bradic M , Carlton JM , Martin DH . Lancet Infect Dis 2018 18 (11) 1251-1259 BACKGROUND: Among women, trichomoniasis is the most common non-viral sexually transmitted infection worldwide, and is associated with serious reproductive morbidity, poor birth outcomes, and amplified HIV transmission. Single-dose metronidazole is the first-line treatment for trichomoniasis. However, bacterial vaginosis can alter treatment efficacy in HIV-infected women, and single-dose metronidazole treatment might not always clear infection. We compared single-dose metronidazole with a 7-day dose for the treatment of trichomoniasis among HIV-uninfected, non-pregnant women and tested whether efficacy was modified by bacterial vaginosis. METHODS: In this multicentre, open-label, randomised controlled trial, participants were recruited at three sexual health clinics in the USA. We included women positive for Trichomonas vaginalis infection according to clinical screening. Participants were randomly assigned (1:1) to receive either a single dose of 2 g of metronidazole (single-dose group) or 500 mg of metronidazole twice daily for 7 days (7-day-dose group). The randomisation was done by blocks of four or six for each site. Patients and investigators were aware of treatment assignment. The primary outcome was T vaginalis infection by intention to treat, at test-of-cure 4 weeks after completion of treatment. The analysis of the primary outcome per nucleic acid amplification test or culture was also stratified by bacterial vaginosis status. This trial is registered with ClinicalTrials.gov, number NCT01018095, and with the US Food and Drug Administration, number IND118276, and is closed to accrual. FINDINGS: Participants were recruited from Oct 6, 2014, to April 26, 2017. Of the 1028 patients assessed for eligibility, 623 women were randomly assigned to treatment groups (311 women in the single-dose group and 312 women in the 7-day-dose group; intention-to-treat population). Although planned enrolment had been 1664 women, the study was stopped early because of funding limitations. Patients in the 7-day-dose group were less likely to be T vaginalis positive at test-of-cure than those in the single-dose group (34 [11%] of 312 vs 58 [19%] of 311, relative risk 0.55, 95% CI 0.34-0.70; p<0.0001). Bacterial vaginosis status had no significant effect on relative risk (p=0.17). Self-reported adherence was 96% in the 7-day-dose group and 99% in the single-dose group. Side-effects were similar by group; the most common side-effect was nausea (124 [23%]), followed by headache (38 [7%]) and vomiting (19 [4%]). INTERPRETATION: The 7-day-dose metronidazole should be the preferred treatment for trichomoniasis among women. FUNDING: National Institutes of Health. |
Where is tuberculosis transmission happening? Insights from the literature, new tools to study transmission and implications for the elimination of tuberculosis.
Auld SC , Shah NS , Cohen T , Martinson NA , Gandhi NR . Respirology 2018 ![]() More than 10 million new cases of tuberculosis (TB) are diagnosed worldwide each year. The majority of these cases occur in low- and middle-income countries where the TB epidemic is predominantly driven by transmission. Efforts to 'end TB' will depend upon our ability to halt ongoing transmission. However, recent studies of new approaches to interrupt transmission have demonstrated inconsistent effects on reducing population-level TB incidence. TB transmission occurs across a wide range of settings, that include households and hospitals, but also community-based settings. While home-based contact investigations and infection control programmes in hospitals and clinics have a successful track record as TB control activities, there is a gap in our knowledge of where, and between whom, community-based transmission of TB occurs. Novel tools, including molecular epidemiology, geospatial analyses and ventilation studies, provide hope for improving our understanding of transmission in countries where the burden of TB is greatest. By integrating these diverse and innovative tools, we can enhance our ability to identify transmission events by documenting the opportunity for transmission-through either an epidemiologic or geospatial connection-alongside genomic evidence for transmission, based upon genetically similar TB strains. A greater understanding of locations and patterns of transmission will translate into meaningful improvements in our current TB control activities by informing targeted, evidence-based public health interventions. |
Finished Whole-Genome Sequences of Clostridium butyricum Toxin Subtype E4 and Clostridium baratii Toxin Subtype F7 Strains.
Halpin JL , Hill K , Johnson SL , Bruce DC , Shirey TB , Dykes JK , Luquez C . Genome Announc 2017 5 (29) ![]() Clostridium butyricum and Clostridium baratii species have been known to produce botulinum toxin types E and F, respectively, which can cause botulism, a rare but serious neuroparalytic disease. Here, we present finished genome sequences for two of these clinically relevant strains. |
Genetic indicators of drug resistance in the highly repetitive genome of Trichomonas vaginalis.
Bradic M , Warring SD , Tooley GE , Scheid P , Secor WE , Land KM , Huang PJ , Chen TW , Lee CC , Tang P , Sullivan SA , Carlton JM . Genome Biol Evol 2017 9 (6) 1658-1672 ![]() Trichomonas vaginalis, the most common non-viral sexually transmitted parasite, causes approximately 283 million trichomoniasis infections annually and is associated with pregnancy complications and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but in a fraction of clinical cases, the parasites can become resistant to this drug. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Reduced representation genome sequencing of approximately 100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium was found to decay rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in genes for which no function has yet been assigned, as well as in functionally-characterized genes relevant to drug resistance (e.g., pyruvate:ferredoxin oxidoreductase). Transcription profiles of resistant strains showed common changes in genes involved in drug activation (e.g., flavin reductase), accumulation (e.g., multidrug resistance pump), and detoxification (e.g., nitroreductase). Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus, a distantly-related species that causes venereal disease in cattle. Shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggest conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool. |
Finished Whole-Genome Sequences of Two Clostridium botulinum Type A(B) Isolates.
Halpin JL , Hill K , Johnson SL , Bruce DC , Shirey TB , Dykes JK , Luquez C . Genome Announc 2017 5 (21) ![]() Clostridium botulinum secretes a potent neurotoxin that causes devastating effects when ingested, including paralysis and death if not treated. In the United States, some clinically significant strains produce toxin type A while also harboring a silent B gene. These are the first two closed genome sequences published for this subset. |
Finished Whole-Genome Sequence of Clostridium argentinense Producing Botulinum Neurotoxin Type G.
Halpin JL , Hill K , Johnson SL , Bruce DC , Shirey TB , Dykes JK , Luquez C . Genome Announc 2017 5 (21) ![]() Here, we present a closed genome sequence for Clostridium argentinense strain 89G, the first strain identified to produce botulinum neurotoxin type G (BoNT/G). Although discovered in 1970, to date, there have been no reference quality sequences publicly available for this species. |
Functional characteristics of health coalitions in local public health systems: Exploring the function of County Health Councils in Tennessee
Barnes P , Erwin P , Moonesinghe R , Brooks A , Carlton EL , Behringer B . J Public Health Manag Pract 2017 23 (4) 404-409 CONTEXT: Partnerships are emerging as critically important vehicles for addressing health in local communities. Coalitions involving local health departments can be viewed as the embodiment of a local public health system. Although it is known that these networks are heavily involved in assessment and community planning activities, limited studies have evaluated whether health coalitions are functioning at an optimal capacity. OBJECTIVE: This study assesses the extent to which health coalitions met or exceeded expectations for building functional capacity within their respective networks. DESIGN: An evaluative framework was developed focusing on 8 functional characteristics of coalitions previously identified by Erwin and Mills. Twenty-nine indicators were identified that served as "proxy" measures of functional capacity within health coalitions. SETTING AND PARTICIPANTS: Ninety-three County Health Councils (CoHCs) in Tennessee. MAIN OUTCOME MEASURE(S): Diverse member representation; formal rules, roles, and procedures; open, frequent interpersonal communication; task-focused climate; council leadership; resources; active member participation; and external linkages were assessed to determine the level of functionality of CoHCs. Scores across all CoHCs were analyzed using descriptive statistics such as frequency distributions, measures of central tendency, and measures of variability. Data were analyzed using SAS 9.3. RESULTS: Of 68 CoHCs (73% response rate), the total mean score for the level of functional characteristics was 30.5 (median = 30.5; SD = 6.3; range, 18-44). Of the 8 functional characteristics, CoHCs met or exceeded all indicators associated with council leadership, tasked-focused climate, and external linkages. Lowest scores were for having a written communications plan, written priorities or goals, and opportunities for training. CONCLUSION: This study advances the research on health coalitions by establishing a process for quantifying the functionality of health coalitions. Future studies will be conducted to examine the association between health coalition functional capacity, local health departments' community health assessment and planning efforts, and changes in community health status. |
Characterizing the genetic diversity of the monkey malaria parasite Plasmodium cynomolgi.
Sutton PL , Luo Z , Divis PC , Friedrich VK , Conway DJ , Singh B , Barnwell JW , Carlton JM , Sullivan SA . Infect Genet Evol 2016 40 243-252 ![]() Plasmodium cynomolgi is a malaria parasite that typically infects Asian macaque monkeys, and humans on rare occasions. P. cynomolgi serves as a model system for the human malaria parasite Plasmodium vivax, with which it shares such important biological characteristics as formation of a dormant liver stage and a preference to invade reticulocytes. While genomes of three P. cynomolgi strains have been sequenced, genetic diversity of P. cynomolgi has not been widely investigated. To address this we developed the first panel of P. cynomolgi microsatellite markers to genotype eleven P. cynomolgi laboratory strains and 18 field isolates from Sarawak, Malaysian Borneo. We found diverse genotypes among most of the laboratory strains, though two nominally different strains were found to be genetically identical. We also investigated sequence polymorphism in two erythrocyte invasion gene families, the reticulocyte binding protein and Duffy binding protein genes, in these strains. We also observed copy number variation in rbp genes. |
Charting a future for epidemiologic training.
Brownson RC , Samet JM , Chavez GF , Davies MM , Galea S , Hiatt RA , Hornung CA , Khoury MJ , Koo D , Mays VM , Remington P , Yarber L . Ann Epidemiol 2015 25 (6) 458-65 ![]() ![]() PURPOSE: To identify macro-level trends that are changing the needs of epidemiologic research and practice and to develop and disseminate a set of competencies and recommendations for epidemiologic training that will be responsive to these changing needs. METHODS: There were three stages to the project: (1) assembling of a working group of senior epidemiologists from multiple sectors, (2) identifying relevant literature, and (3) conducting key informant interviews with 15 experienced epidemiologists. RESULTS: Twelve macro trends were identified along with associated actions for the field and educational competencies. The macro trends include the following: (1) "Big Data" or informatics, (2) the changing health communication environment, (3) the Affordable Care Act or health care system reform, (4) shifting demographics, (5) globalization, (6) emerging high-throughput technologies (omics), (7) a greater focus on accountability, (8) privacy changes, (9) a greater focus on "upstream" causes of disease, (10) the emergence of translational sciences, (11) the growing centrality of team and transdisciplinary science, and (12) the evolving funding environment. CONCLUSIONS: Addressing these issues through curricular change is needed to allow the field of epidemiology to more fully reach and sustain its full potential to benefit population health and remain a scientific discipline that makes critical contributions toward ensuring clinical, social, and population health. |
The origin and diversification of the merozoite surface protein 3 (msp3) multi-gene family in Plasmodium vivax and related parasites.
Rice BL , Acosta MM , Pacheco MA , Carlton JM , Barnwell JW , Escalante AA . Mol Phylogenet Evol 2014 78 172-84 ![]() The genus Plasmodium is a diversified group of parasites with more than 200 known species that includes those causing malaria in humans. These parasites use numerous proteins in a complex process that allows them to invade the red blood cells of their vertebrate hosts. Many of those proteins are part of multi-gene families; one of which is the merozoite surface protein-3 (msp3) family. The msp3 multi-gene family is considered important in the two main human parasites, Plasmodium vivax and Plasmodium falciparum, as its paralogs are simultaneously expressed in the blood stage (merozoite) and are immunogenic. There are large differences among Plasmodium species in the number of paralogs in this family. Such differences have been previously explained, in part, as adaptations that allow the different Plasmodium species to invade their hosts. To investigate this, we characterized the array containing msp3 genes among several Plasmodium species, including P. falciparum and P. vivax. We first found no evidence indicating that the msp3 family of P. falciparum was homologous to that of P. vivax. Subsequently, by focusing on the diverse clade of nonhuman primate parasites to which P. vivax is closely related, where homology was evident, we found no evidence indicating that the interspecies variation in the number of paralogs was an adaptation related to changes in host range or host switches. Overall, we hypothesize that the evolution of the msp3 family in P. vivax is consistent with a model of multi-allelic diversifying selection where the paralogs may have functionally redundant roles in terms of increasing antigenic diversity. Thus, we suggest that the expressed MSP3 proteins could serve as "decoys", via antigenic diversity, during the critical process of invading the host red blood cells. |
The malaria parasite Plasmodium vivax exhibits greater genetic diversity than Plasmodium falciparum.
Neafsey DE , Galinsky K , Jiang RH , Young L , Sykes SM , Saif S , Gujja S , Goldberg JM , Young S , Zeng Q , Chapman SB , Dash AP , Anvikar AR , Sutton PL , Birren BW , Escalante AA , Barnwell JW , Carlton JM . Nat Genet 2012 44 (9) 1046-50 ![]() We sequenced and annotated the genomes of four P. vivax strains collected from disparate geographic locations, tripling the number of genome sequences available for this understudied parasite and providing the first genome-wide perspective of global variability in this species. We observe approximately twice as much SNP diversity among these isolates as we do among a comparable collection of isolates of P. falciparum, a malaria-causing parasite that results in higher mortality. This indicates a distinct history of global colonization and/or a more stable demographic history for P. vivax relative to P. falciparum, which is thought to have undergone a recent population bottleneck. The SNP diversity, as well as additional microsatellite and gene family variability, suggests a capacity for greater functional variation in the global population of P. vivax. These findings warrant a deeper survey of variation in P. vivax to equip disease interventions targeting the distinctive biology of this neglected but major pathogen. |
Plasmodium cynomolgi genome sequences provide insight into Plasmodium vivax and the monkey malaria clade.
Tachibana S , Sullivan SA , Kawai S , Nakamura S , Kim HR , Goto N , Arisue N , Palacpac NM , Honma H , Yagi M , Tougan T , Katakai Y , Kaneko O , Mita T , Kita K , Yasutomi Y , Sutton PL , Shakhbatyan R , Horii T , Yasunaga T , Barnwell JW , Escalante AA , Carlton JM , Tanabe K . Nat Genet 2012 44 (9) 1051-5 ![]() P. cynomolgi, a malaria-causing parasite of Asian Old World monkeys, is the sister taxon of P. vivax, the most prevalent malaria-causing species in humans outside of Africa. Because P. cynomolgi shares many phenotypic, biological and genetic characteristics with P. vivax, we generated draft genome sequences for three P. cynomolgi strains and performed genomic analysis comparing them with the P. vivax genome, as well as with the genome of a third previously sequenced simian parasite, Plasmodium knowlesi. Here, we show that genomes of the monkey malaria clade can be characterized by copy-number variants (CNVs) in multigene families involved in evasion of the human immune system and invasion of host erythrocytes. We identify genome-wide SNPs, microsatellites and CNVs in the P. cynomolgi genome, providing a map of genetic variation that can be used to map parasite traits and study parasite populations. The sequencing of the P. cynomolgi genome is a critical step in developing a model system for P. vivax research and in counteracting the neglect of P. vivax. |
Vaccination of Rhesus macaques with AVA produces a serum antibody response that effectively neutralizes receptor bound protective antigen in vitro
Clement KH , Rudge TL Jr , Mayfield HJ , Carlton LA , Hester A , Niemuth NA , Sabourin CL , Brys AM , Quinn CP . Clin Vaccine Immunol 2010 17 (11) 1753-62 Anthrax toxin (ATx) is comprised of binary exotoxins lethal toxin (LTx) and edema toxin (ETx). They have separate effector proteins (edema factor (EF) or lethal factor (LF)) and share the common binding protein Protective Antigen (PA). PA is the primary immunogen in current licensed vaccine "Anthrax Vaccine Adsorbed" (AVA, Biothrax(R)). AVA confers protective immunity by stimulating production of ATx neutralizing antibodies, which could block the intoxication process at several steps (binding of PA to target cells surface, furin cleavage, toxin complex formation, and binding/translocation of ATx into the cell. To evaluate ATx neutralization by anti-AVA antibodies, we developed two low-temperature LTx neutralization activity (TNA) assays that distinguish antibody blocking before and after binding of PA to target cells (non-complexed (NC) and receptor-bound (RB) TNAs). These assays were used to investigate anti-PA antibody responses in AVA-vaccinated Rhesus macaques (Macaca mulatta) that survived aerosol challenge with Bacillus anthracis Ames spores. Results showed that macaque anti-AVA sera neutralized LTx in vitro, even when PA was pre-bound to cells. Neutralization titers in surviving versus non-surviving animals and between pre-challenge versus post-challenge activity were highly correlated. These data demonstrate that AVA stimulates a myriad of antibodies that recognize multiple neutralizing epitopes, and confirm that change, loss, or occlusion of epitopes after PA is processed from PA83 to PA63 at the cell surface does not significantly affect in vitro neutralizing efficacy. Furthermore, these data support that full length PA83 monomer is an appropriate immunogen for inclusion in next-generation anthrax vaccines. |
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