Large-scale applications of cloning technologies for agriculture: an industry perspective

The present costs and efficiencies of producing cloned embryos, pregnancies and offspring using the simplified nuclear transfer techniques developed in the authors' laboratories are compared with those required for the large-scale application of such cloning technologies in cattle. The current costs in the laboratory of producing large numbers of genetically identical cloned embryos for transfer is around $15.00 per blastocyst, which is within the cost estimated to be commercially viable for cloned female dairy embryos for transfer. However, the pregnancy and calving rates from the transfer of such embryos are still well below that required for large-scale commercial application for which ongoing pregnancy rates of at least 50% per recipient will be required. The current pregnancy rate (30-40 days post-transfer) following the transfer of an average of three cloned embryos per recipient is 37%, and the calving rate 17%, representing high losses between pregnancy diagnosis and term. In the beef industry and in some dairy situations the final product (cloned bulls for natural mating) will have a much higher inherent value and different parameters will therefore apply. Recent developments in the technologies that are likely to increase the probabilities of large-scale application are discussed, including recycling nuclear transfer embryos, somatic cell cloning, new cryopreservation techniques and automated oocyte harvesting.     

Highly effective generic adjuvant systems for orphan or poverty-related vaccines

Safe and effective adjuvants are needed for many vaccines with limited commercial appeal, such as vaccines to infrequent (orphan) diseases or to neglected and poverty-related diseases. Here we found that three nonproprietary liposome formulations containing monophosphoryl lipid A each induced 3-fold to 5-fold increased titers of binding and neutralizing antibodies to anthrax protective antigen compared to aluminum hydroxide-adsorbed antigen in monkeys. All vaccinated monkeys were protected against lethal challenge with aerosolized Ames strain spores.     

A perspective on malaria vaccines

The data obtained with adjuvant—antigen vaccines against asexual malaria parasites in different host—parasite systems are reviewed. From these data the problems associated with antimalarial vaccine development and testing are considered. The requirement for an adjuvant to induce immunity and the type of adjuvant required depends primarily on the host. Since the immune response of man to malaria vaccines is unknown, it is impossible to predict which animal infection is most likely to be a faithful model of malaria in man although it is generally assumed that the monkey is the most appropriate analogue. Therefore careful studies of the immune response of monkeys to purified malarial antigens are needed to develop vaccines for testing in man.     

Opportunities for improving access to vaccines in emerging countries through efficient and aligned registration procedures: An industry perspective

Vaccines play an essential role in preventing infectious diseases. Their registration in importing countries is often cumbersome and unpredictably lengthy, leading to delays in vaccine access for populations that need them most. This report builds on a previous publication identifying challenges for registration of vaccines in emerging countries. As a matter of social responsibility, it was judged necessary to address the challenges and offer a set of solutions for open dialogue. Based on regular exchange of information and experiences, a group of regulatory experts from the vaccine industry developed three sets of proposals for consideration by vaccine stakeholders, with a view to improving the situation, by fostering regulatory convergence, with viable options for streamlining registration procedures through reliance on other experienced regulators or international agencies. Further, it offers options for alignment of structure and contents of Common Technical Document modules and presents a harmonized template application form that could potentially be used by all countries.     

Development of an orphan drug by a start-up company. MetroGel for rosacea.

The Orphan Drug Act of 1983, along with the discovery of a new use for a known drug and an investor willing to assume the necessary risk, brought about the formation of a start-up pharmaceutical company. The primary incentive of the Orphan Drug Act of seven years of marketing exclusivity provided the protection from competition necessary for recovery of the significant research and development and marketing costs. The orphan product, MetroGel, for the treatment of rosacea, required approximately five years of development before it was approved for marketing by the Food and Drug Administration. MetroGel has become the number one drug in the United States for the treatment of rosacea. It currently is marketed in other countries through a licensing agreement with a major pharmaceutical company.     

Development of combination vaccines

Breakthroughs in molecular biology, biochemistry, process development, immunology and related fields have provided the means for improving current vaccines and developing new ones. The increasing availability of these vaccines is providing the unprecedented opportunity to prevent serious infectious disease in different age groups and to significantly reduce associated morbidity and mortality. However, since the great majority of licensed and experimental vaccines in advanced clinical studies are injected, each new vaccine creates the need for additional needlesticks which could become so numerous as to discourage full compliance with immunization schedules. Therefore, the development of combination vaccines is a major way to assure compliance with immunization needs. The leading types of licensed and experimental vaccines which have been or may be made into combination vaccines will be described. In addition, key challenges common to the development of all combination vaccines will be discussed; these include pharmaceutical, immunological, clinical, regulatory, manufacturing, public health and marketing issues. In order to assure timely development and availability of such combination products, these issues must be integrated successfully early in a development program.     

Influenza vaccine viruses and the development of seasonal vaccines: A Japanese perspective

In Japan, the Ministry of Health, Labour and Welfare (MHLW) designates one specific virus strain for each component of the quadrivalent seasonal influenza vaccine, and four domestic manufacturers produce egg-based influenza vaccines with the same formulation (inactivated, split-virus) using uniform vaccine strains. Thus, discussions of the development of effective seasonal influenza vaccines so far has focused solely on the antigenic match between the vaccine strains and epidemic viruses. However, in 2017, the Japanese selection system of vaccine viruses demonstrated that even a candidate vaccine virus that is antigenically similar to the predicted circulating viruses is not necessarily suitable for vaccine production, given lower productivity of the vaccine. Taking this experience into account, the MHLW reformed the scheme of vaccine strain selection in 2018, and instructed the Vaccine Epidemiology Research Group created by the MHLW to probe how the virus strains for the seasonal influenza vaccine should be selected in Japan. In this context, a symposium, entitled “Issues of the Present Seasonal Influenza Vaccines and Future Prospects”, was held as part of the 22nd Annual Meeting of the Japanese Society for Vaccinology in 2018, and subjects related to the influenza vaccine viruses were discussed among relevant administrators, manufacturers, and researchers. This report summarizes the presentations given at that symposium in order to convey the present scheme of vaccine virus selection, the evaluation of the resulting vaccines, and the efforts at new vaccine formulation in Japan. Notably, from March 2022, the MHLW has launched a discussion of the merits of the seasonal influenza vaccines produced by foreign manufacturers.     

Policy development from the industry perspective

The responsibility and burden for implementation of any option for the disposition of low-activity radioactive waste will primarily reside with the industries that generate the waste and those that provide the necessary waste management and disposal services. Unfortunately, there is no general consensus among these industries on the multiple policy issues that are critical to the application of an effective management and disposal program. This paper discusses the various policy issues that affect these industries and the problems that will likely occur during the course of their activities. These policy issues include public and political concern, opposition, and reaction; multiple and sometimes conflicting government agency jurisdiction, regulation, and policy; issues relating to the transition to a new comprehensive system; conflicts between the interests of the various industry groups; and operational, radiation safety, and regulatory implementation issues. For these reasons, the acceptable options may be limited. Case studies of various waste streams are included to show the specific impact and problems that these issues can create.     

Development of dengue DNA vaccines

Vaccination with plasmid DNA against infectious pathogens including dengue is an active area of investigation. By design, DNA vaccines are able to elicit both antibody responses and cellular immune responses capable of mediating long-term protection. Great technical improvements have been made in dengue DNA vaccine constructs and trials are underway to study these in the clinic. The scope of this review is to highlight the rich history of this vaccine platform and the work in dengue DNA vaccines accomplished by scientists at the Naval Medical Research Center. This work resulted in the only dengue DNA vaccine tested in a clinical trial to date. Additional advancements paving the road ahead in dengue DNA vaccine development are also discussed.