Replicating viral vectors as HIV vaccines: summary report from the IAVI-sponsored satellite symposium at the AIDS vaccine 2009 conference.

In October 2009, The International AIDS Vaccine Initiative (IAVI) convened a satellite symposium entitled 'Replicating Viral Vectors for use in AIDS Vaccines' at the AIDS Vaccine 2009 Conference in Paris. The purpose of the symposium was to gather together researchers, representatives from regulatory agencies, and vaccine developers to discuss issues related to advancement of replication-competent viral vector- based HIV vaccines into clinical trials. The meeting introduced the rationale for accelerating the development of replicating viral vectors for use as AIDS vaccines. It noted that the EMEA recently published draft guidelines that are an important first step in providing guidance for advancing live viral vectors into clinical development. Presentations included case studies and development challenges for viral vector-based vaccine candidates. These product development challenges included cell substrates used for vaccine manufacturing, the testing needed to assess vaccine safety, conducting clinical trials with live vectors, and assessment of vaccination risk versus benefit. More in depth discussion of risk and benefit highlighted the fact that AIDS vaccine efficacy trials must be conducted in the developing world where HIV incidence is greatest and how inequities in global health dramatically influence the political and social environment in developing countries.

Replicating viral vectors as HIV vaccines Summary Report from IAVI Sponsored Satellite Symposium, International AIDS Society Conference, July 22, 2007.

At the International AIDS Society Conference on Pathogenesis, Treatment and Prevention held in Sydney, Australia, in July 2007, the International AIDS Vaccine Initiative (IAVI) convened a satellite symposium entitled 'Accelerating the Development of Replicating Viral Vectors for AIDS Vaccines.' Its purpose was to highlight the rationale for accelerating the development of replicating viral vectors for use as vaccines against HIV-1, and to bring together vaccine scientists, regulatory officials, and public health specialists from industrialized and developing nations to discuss the major issues facing the development and testing of replicating viral vector-based vaccines.

Planning for the next pandemic of influenza.

Worldwide influenza pandemics have occurred at irregular and unpredictable intervals throughout history and it is confidently expected that they will continue to occur in the future. It is now recognised that these pandemics result when avian influenza A viruses succeed in adaptation to and transmission between humans. The impact of pandemic influenza is substantial in terms of morbidity, mortality and economic cost and there is the potential for serious social disruption. Influenza vaccines remain the most effective defence against influenza but will be in short supply during a pandemic, as will the new specific anti-influenza drugs, due to the lead-time required for production and rapid spread of the virus. To minimise the impact of pandemics it is imperative to maximise the availability of both vaccines and antivirals and to ensure that they are used optimally. This requires planning at both the international and national levels. The World Health Organization has, therefore, developed a staged plan for responding to a pandemic threat which is based principally on its surveillance program. It has also prepared guidelines to assist national agencies in their planning. However, there may be further options for increasing our preparedness which should also be considered.

Epidemiology of hepatitis B infection in the Western Pacific and South East Asia.

The Western Pacific and South East Asia regions are the largest and most populous of the six World Health Organisation regions and include more than 40 countries. More than 75% of the world's estimated 350 million carriers are located here. The region has therefore provided many insights into the epidemiology, natural history, and control of hepatitis B infection and has been home to the first national control programmes. Hepatitis B is hyperendemic in most countries of the region, with carrier rates ranging from 5-35% except in Australia, New Zealand, and Japan, where the mean carrier rate is less than 2%. Patterns of infection vary considerably from country to country, city to city, and even village to village, and can change with time. Most infections are acquired early in childhood or in early adult life. A variety of control measures are in place and many countries in the region have introduced widespread or universal childhood immunisation policies with significant success. While it is theoretically possible that hepatitis B infection could be eradicated by universal childhood immunisation, there are several biological and practical issues that make this extremely difficult, suggesting that, for the foreseeable future, control may be a more realisable goal.

Immunisation against hepatitis B in Taiwan.

Hepatitis B is hyperendemic in Taiwan; more than 15% of adults are chronic carriers of the virus and longterm sequelae (chronic active hepatitis, cirrhosis, and hepatocellular carcinoma) are common. A national immunisation programme was implemented in 1984 to tackle the problem. This entailed immunisation of newborn children, followed by susceptible school children and young adults. The programme, which has been in place for a decade, has resulted in a pronounced reduction in the prevalence of HBsAg among young children and seems to have led to a reduction in horizontal transmission among older children.

Lombok Hepatitis B Model Immunization Project: toward universal infant hepatitis B immunization in Indonesia.

The Lombok Hepatitis B (HB) Model Immunization Project was the first mass infant HB immunization project in Indonesia. Key aspects were the procurement of low-cost HB vaccine, integration into routine infant immunization services, and delivery of the first dose in the home within 1 week of birth. The project achieved > 90% coverage with 3 doses of vaccine. The prevalence of HB surface antigen was 1.4% in infants who received 3 doses (with the first dose within 7 days of birth) and 3.0% in those who received the first dose > 7 days after birth, compared with a baseline prevalence of 6.2% (P < .001 in each case). Most vaccine failures occurred in children born to HBe antigen-positive mothers. Antibody prevalence and titers did not correlate with protection. HB vaccine can be successfully integrated into the Expanded Programme on Immunization (EPI), strengthening the EPI and significantly reducing chronic HB infection.

Subgrouping of respiratory syncytial virus strains from Australia and Papua New Guinea by biological and antigenic characteristics.

Strains of respiratory syncytial virus from 3 major areas of Australia and Papua New Guinea (PNG) were analyzed for variations in their antigenic and biological properties and in the molecular weights of their major structural proteins. Seventy-eight strains from infants and young children with LRI were collected from 1981-1984. The RSV season in the Australian cities lasted from April through September, with major peaks in July of each year, while the RSV season in tropical PNG was year-round, with small peaks in March and October of each year coinciding with excessive rainfall. Fifty-six strains were analyzed in detail; 40 were typed by time-resolved fluoroimmunoassay with monoclonal antibodies as group A strains and 16 were group B; both groups were concurrent. Three children of one family had sequential RSV infections 13 months apart, and the etiologic group A strain was identical both years in terms of growth and antigenic properties with strain-specific ferret antisera; the second infection was milder in all three children. On average, the group A strains replicated considerably better than group B strains in HEp2 cells, producing 53% more syncytia and 99% higher infectious virus titers in 31% less time in culture. Ten group A and B reference strains exhibited the same growth patterns as the A and B regional strains, respectively. Differences in antigenicity as measured with hyperimmune antisera to prototype Long strain were even greater. Group A strains exhibited a mean 68% greater IFA staining than B strains, a 71% greater EIA reaction, and were neutralized to 69% higher serum titers than B strains. Again, the reference A and B strains included as controls gave patterns identical to those of the regional strains. Finally, the P phosphoprotein had consistently higher molecular weight in A strains (mean 35,900) than B strains (mean 33,100). Small variations in the sizes of the F and G glycoproteins were not sufficient to suggest grouping on this basis.

Hepatitis in the tropics.

Viral hepatitis, caused by one of five different viruses, is an important cause of illness in tropical countries and a significant cause of death. Vaccines against hepatitis A and B are now available and, if used widely, have the potential virtually to eliminate both these diseases (and also hepatitis D). Vaccines against hepatitis C and E are being developed.

Prevalence of hepatitis C antibodies in patients with clotting disorders in Victoria. Relationship with other blood borne viruses and liver disease.

OBJECTIVE: To elucidate the seroepidemiology of hepatitis C in patients with clotting disorders in comparison with other blood borne infections; to examine the effects of hepatitis C on liver function; and to assess the effectiveness of current screening and inactivation procedures used in preventing the transmission of blood borne viruses by clotting factor preparations. DESIGN: A retrospective analysis of the prevalence of antibodies to hepatitis C virus (HCV), hepatitis B virus (HBV) and human immunodeficiency virus (HIV) by means of commercially available enzyme immunoassays (for antibodies to HCV and HIV) or radioimmunoassays (for HBV antibodies and surface antigen). An analysis was made of serum transaminase levels where such information was available and this was correlated with HCV status. PATIENTS AND SETTING: Panels of sera were collected from adults and children with clotting disorders attending two Melbourne haemophilia treatment centres in 1973 (n = 33), 1980 (n = 33), 1984-1985 (n = 111) and 1987-1990 (n = 217) and tested for antibodies to HCV, HBV and HIV. RESULTS: The prevalence of antibodies to HCV in the four panels tested was 45%, 74%, 75% and 76%, and the prevalence of markers of infection with HBV was 66%, 74%, 62% and 65% respectively. No antibodies to HIV were found in sera in Panels I and II but the prevalence in Panels III and IV was 23% and 36% respectively. In subjects in whom liver function test results were available, there was a significant association between the presence of antibodies to HCV and raised transaminase levels. Since heat inactivation of clotting factors was commenced in Australia in 1984, no new cases of transmission of HIV by clotting factors has been detected, but transmission of HCV in 19 subjects and HBV in one subject could not be excluded. CONCLUSIONS: Hepatitis C infection in haemophiliacs has been a very frequent event, and the presence of antibodies to HCV is associated with an increased incidence of raised transaminase levels. Screening and heat inactivation of clotting factors has prevented further HIV transmission, but exposure to HBV and HCV has not been eliminated.

HTLV-I infection in selected populations in Australia and the western Pacific region.

The prevalence of infection with human T lymphotropic virus type I (HTLV-I) in 19,975 blood samples from Australia and the western Pacific was determined by measuring the presence of specific antibody (anti-HTLV-I) by enzyme-linked immunosorbent assay (ELISA) with confirmation by western blot and/or radioimmunoprecipitation techniques. In Australia no evidence of HTLV-I infection was found in injecting drug users, patients with the acquired immunodeficiency syndrome (AIDS), subjects attending a sexually transmitted diseases clinic, female prostitutes, or transfusion recipients. A low prevalence of infection was detected in people with haemophilia (0.5%) and in male homosexuals (0.5%-1%). No antibody was detected in sera from Vanuatu, Kiribati, American Samoa, the Cook Islands, New Caledonia, the Federated States of Micronesia, French Polynesia and Fiji, but a low frequency of anti-HTLV-I was detected in sera from the Solomon Islands (1.2%) and Nauru (0.6%).

The development of hepatitis C antibody shortly after acute icteric non-A non-B hepatitis.

OBJECTIVE: To determine the relationship between the development of hepatitis C antibody (anti-HCV) and the clinical symptoms in acute hepatitis C. DESIGN: Retrospective analysis of sera from patients with acute non-A non-B hepatitis. SETTING AND PATIENTS: Patients admitted to Fairfield Hospital with the diagnosis of acute non-A non-B hepatitis between 1979 and 1989. Inclusion criteria included a typical clinical illness, accompanied by an alanine aminotransferase level of more than 2.5 times the upper limit of normal (normal, less than or equal to 40 U/L) and negative serological test results for acute hepatitis A and B. MAIN OUTCOME MEASURE: Time to develop anti-HCV after the onset of symptoms in patients with acute hepatitis C. RESULTS: Seroconversion was demonstrated in 26 of the 128 patients who fulfilled the inclusion criteria. In these patients, antibody was detected between one week and 32 weeks after the onset of dark urine; more than half the patients (54%) had seroconverted by four weeks and a third (34%) developed antibodies within two weeks. Of 20 patients who had sera collected within four weeks of the onset of dark urine, 14 (70%) had developed antibody. CONCLUSION: These results suggest that in patients with community-acquired hepatitis C, seroconversion occurs significantly earlier than is observed in patients who have been infected by blood transfusion. Sera taken shortly after the onset of symptomatic hepatitis C may be useful in the diagnosis of this condition.