Day 1 :
Griffith University, Australia
Time : 09:30-10:00
Professor Allan Cripps is recognised internationally for his research in the field of mucosal immunology. Much of this work has been directed towards mucosal immunisation against a range of bacterial pathogens, particularly those of the respiratory tract. He has published extensively in the peer reviewed literature, presented his research findings at numerous international scientific and medical conferences and has been the recipient of a large number of competitive government and industry research grants. In addition, Professor Cripps has a significant patent portfolio in the fields of diagnostics and vaccine candidate protein antigens. Professor Cripps is currently the executive head of the Health Faculty at Griffith University and maintains his keen interest in mucosal immunology and respiratory tract infections. He is also the Editor in Chief of the journal pneumonia and is an active member of a number of committees and Boards in the fields of immunology, infectious diseases and vaccinology. In 2015 he was awarded the Order of Australia (AO) for distinguished service to tertiary education as a senior administrator, and to public health as a leading immunologist, academic and researcher in the area of mucosal immunisation.
Induction of mucosal immune responses best occur through priming of mucosal associated lymphoid aggregates that selectively sample the milieu bathing the mucosal surfaces. Despite considerable research and the advantages of mucosal immunisation, few oral vaccines are routinely available for use today with the results of many oral vaccine trials being variable and suboptimal at best. Over the last three decades our group has undertaken extensive studies in animal models and in human trials to develop an effective oral vaccine against respiratory tract infections caused by non-typeable Haemophilus influenzae (NTHi) and Pseudomonas aeruginosa. Human studies have focused on subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. Animal studies of acute and chronic respiratory infection models have provided proof of concept pre-clinical data and significant knowledge about the immunological mechanisms induced by mucosal immunisation. Oral immunisation of subjects with COPD against NTHi has resulted in a significant reduction in acute exacerbations, hospitalisation and antibiotic prescriptions. For P aeruginosa, administration of an oral whole killed cell vaccine reduced number of P. aeruginosa cultured from sputum and induced a functional antibody response against the vaccine strain in subjects with bronchiectasis. These studies clearly demonstrate that oral immunisation should be considered as an effective route of vaccination for infections of the respiratory tract.
- Track 1: Technologies for The Design, Discovery, Formulation and Administration of Vaccines
Track 5: Recent Advances in Animal Vaccination
Track 6: Adjuvants for Human/ Animal Vaccines—Current Status, Problems and Future prospects
Track 9: Advancements in Vaccine Development: Diseases and Infections
QIMR Berghofer Medial Research Institute, Australia
Time : 10:45-11:10
Denise Doolan is a molecular immunologist who heads the Molecular Vaccinology Laboratory at the QIMR Berghofer Medical Research Institute. She is an NHMRC Principal Research Fellow and was previously a Pfizer Australia Senior Research Fellow. Her research investigates the molecular basis of immunity, with a focus on malaria and rational vaccine development. Her research program encompasses core themes of: (i) immune mechanisms; (ii) antigen and epitope discovery from genomic sequence data; and (iii) molecular vaccine technologies. She has published over 120 research articles, is an inventor on a number of patents, and has been a consultant for a number of biotechnology companies.
Vaccines are the most efficient health care intervention for global public health but vaccines against many diseases caused by complex pathogens are still not available despite intense research. A significant advance of the past decade has been the elucidation of the genome, proteome and transcriptome of many pathogens. These datasets provide the foundation for genome-based approaches to identify target antigens for rational vaccine design. Using malaria as a model, we are pursuing a multi-pronged approach using technology platforms including protein microarrays, high throughput protein production, and epitope prediction algorithms, with specimens from humans, or animals naturally or experimentally exposed to malaria. We have established that T cell and antibody responses to the Plasmodium parasite are broadly distributed throughout the proteome, and have identified many novel antigens that are more immunogenic than antigens currently considered as high priority vaccine antigens. Importantly, the subsets of antigens preferentially recognized by T cells are distinct from the subset targeted by antibodies. We have further integrated and analyzed our comprehensive antibody and T cell datasets to identify specific features associated with antibody or T cell immune reactivity. Our data significantly expand our knowledge base of targets of host-parasite immunity and suggest that distinct vaccine approaches and antigen targets are required depending on whether antibodies or T cells are the desired vaccination outcome. Such genome-based vaccine approaches may overcome the problem of poorly efficacious vaccines that has plagued vaccine developers for many years.
Time : 11:10-11:35
Filip Dubovsky is a Vice President in Clinical Biologics and the Therapeutic Area Head for Infectious Disease and Vaccines at MedImmune/AstraZeneca. He has a BA in cell biology from Cornell University, a MD from the University of Alabama and a MPH from John’s Hopkins University. He completed his pediatric training at Stanford University, Pediatric Infectious Disease Fellowship at the Center for Vaccine Development at the University of Maryland and Preventive Medicine training at Johns Hopkins University.
Maternal vaccination has advanced as an approach to protect newborns against neonatal diseases. An alternative to maternal vaccination is passive vaccination using monoclonal antibodies (mAbs). Advances in mAb potency, extended half-life technology and manufacturing techniques allows for the development of monoclonal antibodies that can be used as passive vaccines in infants. MEDI8897 is a passive RSV vaccine for preterm and term infants. The optimization of a human derived mAb led to a 200-fold improvement of in vitro potency compared to palivizumab. Mutations in the Fc region have enabled a 3-fold increase in antibody half-life compared to standard IgG. In combination, these advances have resulted in a mAb that can be used as a passive vaccine to protect infants through an entire RSV transmission season with a single fixed intramuscular dose. MEDI8897 was evaluated in healthy adult volunteers (N=136). A range of intravenous and intramuscular doses were evaluated: the safety profile was favorable, and the mean half-life was extended to 67-80 days across all dosage groups. Anti-drug antibody was low and did not impact the pharmacokinetics. The safety and pharmacokinetic profile supported advancement of MEDI8897 into infant clinical studies. In temperate climates with a discreet RSV season, MEDI8897 can be used at the beginning of respiratory viral season to protect infants entering their first RSV season. In tropical climates, where the RSV transmission can be prolonged, MEDI8897 can be used as a birth-dose to protect newborns for the first six months of life where the risk of severe disease is greatest
Instituto de Investigacion Marques de Valdecilla Avda, Spain
Title: A dendritic cell-targetted vaccine loaded with a glyceraldehyde-3-phosphate dehydrogenase peptide confers wide protection to listeriosis in susceptible and resistant mice
Time : 11:35-12:00
Carmen Alvarez-Dominguez has completed her Ph.D at the age of 29 years from Universidad Autonoma de Madrid and postdoctoral studies from Washington University School of Medicine on Small GTPases role in Listeria monocytogenes phagocytosis. She is the director of the Group on Genomics, Proteomics and Vaccines at the Research Institute Marqués de Valdecilla (IDIVAL) in Santander, Spain. She has published more than 26 papers in reputed journals and serving as an editorial board member of Microbes and Infection and OMICS. She also is coauthor of the patent: Immunogenic peptides against Listeria and Mycobacterium, antibodies and their uses with reference PCT/ES2007/070144.
Susceptible and resistant mice to listeriosis are convenient models to examine vaccines efficiency since they mimic human diversity. Dendritic cells (DC) vaccines loaded with immunogeneic peptides are powerful tools for the vaccination against intracellular bacteria. To produce a vaccine against the human bacterial pathogen, Listeria monocytogenes, we assessed DC loaded with immunogenic listeriolysin O (LLO) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) peptides. Our approach consisted on examining DC-LLO or DC-GAPDH vaccines coupled with peptides with different binding capacities to MHC molecules in susceptible or resistant mice. DC-GAPDH1-22 vaccines that contained weak binding sequences to IAb and IAd MHC class II molecules and medium binding sequences to H-2Kb and H-2Kd MHC class I molecules, provided the best protection to listeriosis in susceptible and resistant mice. DC-LLO91-99 vaccines loaded with a strong peptide binder to H-2Kd but weak binder to H-2Kb MHC class I molecules, conferred better protection than DC-LLO296-304 vaccines loaded exclusively with a strong peptide binder to H-2Kb. DC-LLO190-201, DC-LLO189-200 and DC-LLO189-201 vaccines loaded exclusively with weak peptide binders to IAb and IAd MHC class II molecules, respectively, presented no significant protection. Enhanced protection in listeriosis correlated with increased splenic CD8+ DC, enhanced IL-12 and expansion of Listeria antigen specific CD8+ and CD4+ T cells producing IFN-. DC-GAPDH1-22 vaccines that combine any type of CD8+ epitopes and CD4+ weak binder epitopes conferred higher protection to listeriosis in susceptible and resistant mice, than DC-LLO91-99 or DC-LLO296-304 vaccines that include exclusively CD8+ epitopes. DC-GAPDH1-22 vaccines could be an effective vaccine for prophylactic protection against human listeriosis in susceptible and resistant individuals.
The University of Queensland, Queensland Alliance for Agriculture and Food Innovation, Australia
Title: Development and assessment of multivalent recombinant vaccines for bovine respiration disease
Time : 12:00-12:25
A/Prof Mahony received his PhD in molecular biology from James Cook University. He is a molecular virologist who joined the University of Queensland in 2010 after 15 years working with the AgriScience Queensland. A/Prof Mahony's research interests include the characterisation of animal pathogens and how they interact with their respective hosts. By better understanding disease development his research is improving disease prevention and management in livestock industries. His research has been published in international journals and has been subjected to patenting. A/Prof Mahony currently leads research projects developing vaccines for bovine respiratory disease and cattle ticks.
Bovine respiratory disease (BRD) is the most important cause of morbidly and mortality in intensively finished cattle in the world. The total economic losses attributed to BRD have been estimated to exceed US$1 billion annually. The disease has a complex aetiology involving a range of viral and bacterial pathogens, animal factors and environmental conditions all contributing to BRD development. It has been demonstrated that prior exposure to specific pathogens can reduce the risk of cattle developing BRD which suggests that vaccines could play a role in ameliorating the impacts of this disease. However the range of pathogens implicated in BRD presents significant challenges in the development of effective vaccines. Currently there are four viruses and three bacteria commonly implicated in BRD development. Furthermore the meaningful assessment of vaccine efficacy in the context of such complex disease aetiology can also be problematic. To address these issues the development of multivalent live viral vaccines has been undertaken using a bovine herpesvirus 1 infectious clone to deliver antigens from other BRD pathogens. In addition the capacity of these prototype vaccines to protect cattle from BRD are being assessed in biphasic multi-pathogen challenge models to more accurately assess field efficacy. The progress towards achieving these goals and ultimately improved control of BRD will be discussed.
Lunch Break & Networking: 12:25-13:45
Australian Infectious Diseases Research Centre, Australia
Title: Advax-adjuvanted killed Japanese encephalitis virus (JEV) vaccine is safe in pregnant mares and in foals and induces robust immunological memory.
Time : 13:45-14:10
Helle Bielefeldt-Ohmann is a veterinary pathologist focusing on the pathogenesis of infectious diseases, in particular zoonotic diseases and virus infections causing neuropathology. Bielefeldt-Ohmann is championing the use of ‘natural animal models’ for studies of infectious diseases of importance to both human and animal health as part of the concept “One World Medicine”. Her current research activities are mainly focused on the pathogenesis of flavivirus-induced encephalitis and foetal encephalopathy, melioidosis and tuberculosis. Other infectious diseases of interest include rhadinovirus induced neoplasia and vasculopathy.
In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAXTM) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74-152 days old, received two injections of JE-ADVAXTM. The vaccine was safe and well-tolerated and induced a strong JEV-neutralizing antibody response in all foals. MVEV and WNVKUN antibody cross-reactivity was seen in 33% and 42% of the immunized foals, respectively. JE-ADVAXTM was also safe and well-tolerated in pregnant mares and induced high JEV-neutralizing titers. The neutralizing activity was passively transferred to their foals via colostrum. Foals that acquired passive immunity to JEV via maternal antibodies then were immunized with JE-ADVAXTM at 36-83 days of age, showed evidence of maternal antibody interference with low peak antibody titers post-immunization when compared to immunized foals of JEV-naïve dams. Nevertheless, when given a single JE-ADVAXTM booster immunization as yearlings, these animals developed a rapid and robust JEV-neutralizing antibody response, indicating that they were successfully primed to JEV when immunized as foals, despite the presence of maternal antibodies. Overall, JE-ADVAXTM appears safe and well-tolerated in pregnant mares and young foals and induces protective levels of JEV neutralizing antibodies with partial cross-neutralization of MVEV and WNVKUN.
Director Institute of Immunology, China
Time : 14:10-14:35
Yuzhang Wu has completed his Ph.D for Immunology at the age of 29 years from Third Military Medical University School of Medicine. He is the director of the Institute of Immunology, PLA, the Chair of National Engineering Lab for Vaccine Development of China and National Center for Immunoproducts Research and Development of China. He has published more than 150 papers in reputed journals, applied for 75 international and national invention patents, among which 43 has been approved; and has gained 2 item of Computer software copyright. He is serving as chief-editor of Immunological Journal
As chronic diseases, such as tumor, persistent infections, autoimmune diseases, cognitive diseases and metabolic disorders, are the main health problems at present for human, there is a clear need for postexposure vaccines, most of which are therapeutic. To date few postexposure vaccines have been licensed to industry, although large amount of studies had been conducted in the past 20 years. There is a clear indication of the era of transformational development of vaccine. For postexposure vaccine development, we need clear target, novel strategy, and new technologies in vaccine design, adjuvant, and delivery systems. From the view of immunology, there are several challenges: Heterologous immunity, narrowed TCR repertoire, individual TCR usage, cross and pathologic reactivity, antigen load and heterologous immunity, immune deviation. This talk will summarize recent achievements in post-exposure vaccinology development and insight into challenges in immunology.
University of British Columbia, Canada
Time : 14:35-15:00
The global persistence of tuberculosis (TB) epidemic and the current spread of drug resistant M. tuberculosis (Mtb) strains have stimulated an unprecedented rush to develop novel efficient vaccines. An important strategy toward this goal remains improving the efficacy of current BCG vaccine based upon its remarkable safety record during almost 100 year of massive human immunization. Current strategies to improve BCG attempt to over-express genes encoding specific Mtb antigens and/or regulators of antigen presentation function, which indeed have the potential to reshape BCG in many ways. However, these approaches often face serious difficulties, in particular the efficiency and stability of gene expression via nucleic acid complementation and safety concerns associated with the introduction of exogenous DNA, in particular antibiotic resistant genes, into human cells and tissues. As an alternative, we developed a novel non-genetic approach for rapid and efficient display of exogenous proteins on bacterial cell surface. The technology involves expression of proteins of interest in fusion with a mutant version of monomeric avidin that has the feature of reversible binding to biotin. Fusion proteins are then used to decorate the surface of biotinylated BCG. Chimeric proteins corresponding to a surrogate antigen derived from ovalbumin and to a fusion of Mtb antigens ESAT6/TB10.4 were generated and tested for immunogenicity functions. We found that modified BCG strains displaying ovalbumin antigen or ESAT6/TB10.4 induce an immune response in the mouse similar to that induced by BCG genetically expressing the same antigens. This novel technology, therefore, represents a practical and effective alternative to DNA-based gene expression for upgrading the current BCG vaccine.
Queensland University of Technology, Australia
Time : 15:00-15:30
Ken Beagley completed his PhD at the University of Otago and is a Professor of Immunology and Deputy Director at the Institute of Health and Biomedical Innovation at Queensland University of Technology. He has worked in the area of mucosal and reproductive immunology for the past 25 years at the University of Alabama at Birmingham and the University of Newcastle prior to moving to QUT. He has over 200 publications, is on the editorial boards of Mucosal Immunology, Vaccine and Journal of Reproductive Immunology and is the current president of the Society for Mucosal Immunology.
Chlamydia trachomatis is the most common STI in Australia. Current antibiotic therapies have not halted the increased incidence (4-fold in the past decade) and no vaccine is currently available. Infection-induced inflammation causes pelvic inflammatory disease, ectopic pregnancy and infertility in women, the most expensive outcomes of chlamydial infection and may also compromise male fertility. Protective immunity against Chlamydia requires a strong mucosal Th1 response together with mucosal antibodies. We have used a mouse model to evaluate different adjuvants and mucosal routes of vaccine delivery, combined with the major outer membrane protein antigen (MOMP) in order to elicit protection against both infection and inflammatory disease of the female reproductive tract. The magnitude and duration of infection was reduced by intranasal, sublingual and transcutaneous vaccine delivery of MOMP with different adjuvants, however intranasal immunisation with either Iscomatrix® or a combination cholera toxin/CpG (CT/CpG) adjuvant provided the greatest protection against infection. Interestingly, sublingual immunisation using the CTA1-DD adjuvant plus MOMP protected against inflammatory disease without preventing ascending infection while intranasal immunisation with the CT/CpG adjuvant prevented ascending infection but not the development of inflammatory disease. Intranasal immunisation of mice with a combination of antigens, selected from different stages of the chlamydial developmental cycle, combined with Iscomatrix® protected mice against both ascending infection and inflammatory oviduct damage. Our data suggest that chlamydial disease is independent of the infectious burden and that it is possible to develop vaccines that protect against inflammatory damage even in the absence of sterilising immunity.
Prof Suhrbier is a Group Leader at the Inflammation Biology, QIMR B, Australia www.qimrberghofer.edu.au/page/Lab/Inflammation_Biology/. He has 140 international peer reviewed publications, 5794 citations (H index 44) and 17 patents, 6 cover products, 2 are in phase II trials. Publications can be found on http://scholar.google.com.au/citations?hl=en&user=KxKWgxwAAAAJ&view_op=list_works&sortby=pubdate.
Chikungunya virus is a mosquito borne alphavirus (related to the Australian Ross River virus) which has recently re-emerged to produce the largest epidemic ever recorded for this virus, with recent outbreaks in the Caribbean (with an estimated 1 million cases) and in Papua New Guinea and the Pacific Islands. The virus produces a predominantly rheumatic disease, with acute and chronic polyarthritis/polyarthralgia the dominate symptom. A range of vaccines have been developed, with neutralising antibodies against the E1/E2 heterotrimeric surface glycoproteins appearing to be sufficient for protection against viraemia and disease. Although correlates of protection appear clear, the pernicious nature of outbreaks presents a major hurdle for commercial vaccine development. Epidemics of chikungunya virus disease have emerged every 2-50 years, with all continents (aside from Antarctica) affected by one or more outbreak; such epidemiology clearly complicates logistics associated with vaccine testing and deployment 1. The main disease burden is arguably the chronic rheumatic disease, which can last months, occasionally over a year. Chronic disease appears to be due to the persistence of viral RNA and protein in joint tissues, with macrophages believed to be the cell type involved 2. Why the normally robust host immune response is unable to clear the virus is unclear. Whether therapeutic vaccines might help clear persistent virus is also unclear. References: 1. Suhrbier et al. 2012. Arthritogenic alphaviruses - an overview. Nat Rev Rheumatol. 8(7):420-9. 2. Poo et al. 2014. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection. PLoS Negl Trop Dis. 8(12):e3354
Time : 16:10-16:35
Alexander Khromykh received his BSc degree in Physiology from the Tomsk State University, Russia, and his PhD degree in Molecular Virology from the State Centre for Virology and Biotechnology "Vector”, Russia. He worked as Postdoctoral Fellow at the University of Ottawa in Canada. He then joined Sir Albert Sakzewski Virus Research Centre in Brisbane in 1992 and became a laboratory Head in 2001. He was awarded NH&MRC Senior Research Fellowship in 2004 and moved his laboratory to St Luica campus in 2005 to take an appointment with SCMB. He was the founding Director of the SCMB’s Centre for Infectious Disease Research and is currently the Deputy Director of the Australian Infectious Diseases Research Centre, an NH&MRC Senior Research Fellow and Professor of Virology at SCMB.
Recent unprecendented outbreak of Ebola virus (EBOV) in West Africa which reportedtly infected more than 27,000 people and killed more than 11,000 of them has prompted an urgent need for vaccine. Although a number of EBOV vaccine candidates have been developed and some of them are currently undergoing clinical trials, none of them have yet been approved. We have been developing EBOV vaccine candidate based on self-replicating RNA (replicon) of naturally attenuated strain of West Nile virus, Kunjin (KUN). As an antigen we use glycopprotein GP from EBOV Zaire strain. KUN-GP replicon RNA was packaged into virus-like particles (VLPs) by KUN structural proteins produced in a packaging cell line. D637L mutant of GP with enhanced shedding produced less cytopathicity than wt GP during VLP preparation and allowed generation of higher VLP titres. Two immunizations of guniea pigs with 5 x 106 KUN-GP VLPs using either wt GP or D637L mutant GP resulted in up to 85% protection against challenge with 200 LD50 of guinea pig-adapted EBOV. Further vaccine efficacy studies were performed in African green monkeys. Four anilams were vaccinated twice with 109 KUN-GP D637L VLPs with 4 week interval and 3 weeks after the second immunization they were challenged with 600 pfu of Zaire EBOV. Three animals were completely protected against EBOV challenge, while one vaccinated animal and the control animal died from infection. We suggest that KUN replicon VLPs encoding EBOV GP/D637L represent a viable EBOV vaccine candidate.
University of Jember, Indonesia
Title: Future prospect of mosquito salivary components as novel target for vector based vaccine against Dengue: molecular characterization of immunomodulatory protein from salivary glands of Aedes aegypti
Time : 16:35-17:00
Kartika Senjarini has completed his PhD (Dr. rer. nat) at the age of 32 years from The University of Rostock – Germany. She had the opportunity to do postdoctoral studies at The University of Kassel, Germany as well as at International Vaccine Institute, South Korea. Apart from her responsibility as principle investigator in the Transmission Blocking Vaccine’s Research Group at her Department, she is currently also appointed as Head of Biology Department, Faculty of Mathematic & Natural Sciences, The University of Jember Indonesia.
Dengue Fever (DF) Virus-based Vaccine development showed a relatively slow progress because it should induce protection against the 4 serotypes of Dengue Viruses and there is a very limited adequate animal model for dengue virus infection. In the last decade, new approach in vaccine development for arthropode-borne diseases is using salivary vector components. This approach based on hyphotesis that arthropode vectors saliva contains vasomodulator and imunomodulator proteins that could enhance pathogen infection. Therefore, it should be possible to control pathogen transmission by vaccinating the host against the molecule(s) in saliva that potentiate the infection, thereby blocking the enhancing effects of saliva and thus preventing the pathogen from establishing infection in the host (Transmission Blocking Vaccine, TBV). However, specific component as a potential target for TBV in Aedes aegypti, as major vector for DF has not yet been identified so far. This paper wanted to elaborate the immunogenic components from Salivary Gland (SG) of Aedes aegypti as potential immunomodulatory protein. We have characterized 2 immunogenic proteins that are only recognized by healthy people living in endemic area and not by people from non-endemic area. They have molecular weight of 31 & 56 kD. Further molecular characterization by Mass-Spectrophotometry of those proteins showed that 31 kDa and dan 56 kDa have high similarity with D7-Protein Family (Odorant Binding Protein) & Apyrase, respectively. These proteins have very important role in vector blood feeding process. This also supported by the strong immunogenicity of 31 kDa against human sera in healthy people as well as Dengue patients. The apyrase activity of 56 kD protein has also been proven in this research.
The University of Melbourne, Australia
Title: Using carriage surveillance to show direct and indirect effects of pneumococcal conjugate vaccine
Time : 17:00-17:20
Associate Professor Fiona Russell is a paediatrician with qualifications in public health and epidemiology. She completed her PhD evaluating alternative pneumococcal vaccination schedules in infants in Fiji. The findings informed the pneumococcal conjugate vaccine (PCV) schedules in the latest WHO PCV position paper. She was awarded both the Chancellor and Dean's Prize for PhD Excellence by The University of Melbourne. She has undertaken consultancies for WHO, UNICEF, and Australian Aid in the Asia-Pacific region, and Africa on the disease burden of vaccine preventable diseases, new vaccine introduction, and maternal and child health policies to reduce child mortality and improve maternal health.
Pneumonia is the commonest reason why child die worldwide. It is estimated that one-third of all pneumonia deaths are due to the pneumococcus. Few countries in the Aisa-Pacific region have introduced pneumococcal conjugate vaccine (PCV) and there are few data from this region on the direct or indirect effects of PCV. In this study in Lao PDR, PNG, and Mongolia we will assess the direct and indirect effects of PCV13 on the nasopharyngeal (NP) pneumococcal carriage of children hospitalised with acute respiratory infection. Following PCV13 introduction, a reduction in PCV13 serotype NP carriage is likely to translate into a reduction in pneumococcal disease, and be a marker of direct and indirect immunity. We will use NP carriage surveillance amongst children with acute respiratory infection to estimate the PCV13 coverage required to demonstrate direct and indirect immunity by showing a sustained decline in PCV13 serotype carriage. This study will demonstrate how carriage surveillance in children with pneumonia can be used to estimate the PCV coverage required to show evidence of herd immunity, and monitor the vaccine’s impact on carriage, and thereby provide information for national planners to maximise the effectiveness of their immunisation programs.