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Influenza viruses cause a significant number of infections and deaths annually. In addition to seasonal infections, the risk of an influenza virus pandemic emerging is extremely high owing to the large reservoir of diverse influenza viruses found in animals and the co-circulation of many influenza subtypes which can reassort into novel strains. Development of a universal influenza vaccine has proven extremely challenging. In the absence of such a vaccine, rapid response technologies provide the best potential to counter a novel influenza outbreak. Here, we demonstrate that a modular trimerization domain known as the molecular clamp allows the efficient production and purification of conformationally stabilised prefusion hemagglutinin (HA) from a diverse range of influenza A subtypes. These clamp-stabilised HA proteins provided robust protection from homologous virus challenge in mouse and ferret models and some cross protection against heterologous virus challenge. This work provides a proof-of-concept for clamp-stabilised HA vaccines as a tool for rapid response vaccine development against future influenza A virus pandemics.

Background: Given the scale of the ongoing COVID-19 pandemic, the development of vaccines based on different platforms is essential, particularly in light of emerging viral variants, the absence of information on vaccine-induced immune durability, and potential paediatric use. We aimed to assess the safety and immunogenicity of an MF59-adjuvanted subunit vaccine for COVID-19 based on recombinant SARS-CoV-2 spike glycoprotein stabilised in a pre-fusion conformation by a novel molecular clamp (spike glycoprotein-clamp [sclamp]). Methods: We did a phase 1, double-blind, placebo-controlled, block-randomised trial of the sclamp subunit vaccine in a single clinical trial site in Brisbane, QLD, Australia. Healthy adults (aged ≥18 to ≤55 years) who had tested negative for SARS-CoV-2, reported no close contact with anyone with active or previous SARS-CoV-2 infection, and tested negative for pre-existing SARS-CoV-2 immunity were included. Participants were randomly assigned to one of five treatment groups and received two doses via intramuscular injection 28 days apart of either placebo, sclamp vaccine at 5 μg, 15 μg, or 45 μg, or one dose of sclamp vaccine at 45 μg followed by placebo. Participants and study personnel, except the dose administration personnel, were masked to treatment. The primary safety endpoints included solicited local and systemic adverse events in the 7 days after each dose and unsolicited adverse events up to 12 months after dosing. Here, data are reported up until day 57. Primary immunogenicity endpoints were antigen-specific IgG ELISA and SARS-CoV-2 microneutralisation assays assessed at 28 days after each dose. The study is ongoing and registered with ClinicalTrials.gov, NCT04495933. Findings: Between June 23, 2020, and Aug 17, 2020, of 314 healthy volunteers screened, 120 were randomly assigned (n=24 per group), and 114 (95%) completed the study up to day 57 (mean age 32·5 years [SD 10·4], 65 [54%] male, 55 [46%] female). Severe solicited reactions were infrequent and occurred at similar rates in participants receiving placebo (two [8%] of 24) and the SARS-CoV-2 sclamp vaccine at any dose (three [3%] of 96). Both solicited reactions and unsolicited adverse events occurred at a similar frequency in participants receiving placebo and the SARS-CoV-2 sclamp vaccine. Solicited reactions occurred in 19 (79%) of 24 participants receiving placebo and 86 (90%) of 96 receiving the SARS-CoV-2 sclamp vaccine at any dose. Unsolicited adverse events occurred in seven (29%) of 24 participants receiving placebo and 35 (36%) of 96 participants receiving the SARS-CoV-2 sclamp vaccine at any dose. Vaccination with SARS-CoV-2 sclamp elicited a similar antigen-specific response irrespective of dose: 4 weeks after the initial dose (day 29) with 5 μg dose (geometric mean titre [GMT] 6400, 95% CI 3683–11 122), with 15 μg dose (7492, 4959–11 319), and the two 45 μg dose cohorts (8770, 5526–13 920 in the two-dose 45 μg cohort; 8793, 5570–13 881 in the single-dose 45 μg cohort); 4 weeks after the second dose (day 57) with two 5 μg doses (102 400, 64 857–161 676), with two 15 μg doses (74 725, 51 300–108 847), with two 45 μg doses (79 586, 55 430–114 268), only a single 45 μg dose (4795, 2858–8043). At day 57, 67 (99%) of 68 participants who received two doses of sclamp vaccine at any concentration produced a neutralising immune response, compared with six (25%) of 24 who received a single 45 μg dose and none of 22 who received placebo. Participants receiving two doses of sclamp vaccine elicited similar neutralisation titres, irrespective of dose: two 5 μg doses (GMT 228, 95% CI 146–356), two 15 μg doses (230, 170–312), and two 45 μg doses (239, 187–307). Interpretation: This first-in-human trial shows that a subunit vaccine comprising mammalian cell culture-derived, MF59-adjuvanted, molecular clamp-stabilised recombinant spike protein elicits strong immune responses with a promising safety profile. However, the glycoprotein 41 peptide present in the clamp created HIV diagnostic assay interference, a possible barrier to widespread use highlighting the criticality of potential non-spike directed immunogenicity during vaccine development. Studies are ongoing with alternative molecular clamp trimerisation domains to ameliorate this response. Funding: Coalition for Epidemic Preparedness Innovations, National Health and Medical Research Council, Queensland Government, and further philanthropic sources listed in the acknowledgments.

Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace with more than 30 candidate vaccines now in clinical evaluation. Here we describe the preclinical development of an adjuvanted, prefusion-stabilised Spike (S) protein “Sclamp” subunit vaccine, from rational antigen design through to assessing manufacturability and vaccine efficacy. In mice, the vaccine candidate elicits high levels of neutralising antibodies to epitopes both within and outside the receptor binding domain (RBD) of S, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells. We also show protection in Syrian hamsters, which has emerged as a robust animal model for pulmonary SARS-CoV-2 infection. No evidence of vaccine enhanced disease was observed in animal challenge studies and pre-clinical safety was further demonstrated in a GLP toxicology study in rats. The Sclamp vaccine candidate is currently progressing rapidly through clinical evaluation in parallel with large-scale manufacture for pivotal efficacy trials and potential widespread distribution.

Efforts to develop and deploy effective vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continue at pace. Here we describe rational antigen design through to manufacturability and vaccine efficacy, of a prefusion-stabilised Spike (S) protein, Sclamp. This strategy uses an orthogonal stabilisation approach compared to canonical vaccines, in combination with the licensed adjuvant MF59 (Seqirus). In mice, the Sclamp vaccine elicits high levels of neutralising antibodies, as well as broadly reactive and polyfunctional S-specific CD4+ and cytotoxic CD8+ T cells in vivo. In the Syrian hamster challenge model (n = 70), vaccination results in reduced viral load within the lung, protection from pulmonary disease, and decreased viral shedding in daily throat swabs which correlated strongly with the neutralising antibody level. The Sclamp vaccine candidate is currently completing Phase 1 clinical evaluation, in parallel with large-scale commercial manufacture for pivotal efficacy trials and potential widespread distribution. Funding: This work was funded by CEPI. Conflict of Interest: K.J.C., D.W. and P.R.Y. are inventors of the “Molecular Clamp” patent, US 2020/0040042.

The present study provides a life style profile of the early adopter of cable television service. A questionnaire was administered to 600 householders from which 149 were later identified as early adopters and 238 as non-adopters. The early adopters were found to be younger, have a higher annual income and more children at home aged 11 to 15. They were more achievement oriented, more individualistic, more materialistic, and possessed greater self-esteem than the non-adopters. They were greater users of the media in general and of television in particular.

Little attention has been paid to prospective customers who defect before buying. This paper examines the almost customer phenomenon. It reviews literature on service quality, customer satisfaction, retention, relationships, loyalty and defection. It also categorizes the causes of almost customer experiences into a series of themes. The almost customer phenomenon and its effects are presented in the context of implications for managers and for future research. The almost customer phenomenon may appear to be a study of early customer defection, but the almost customer defects before buying. The customer defection literature assumes that a firm has attracted customers. But, not every attempted transaction leads to a purchase. Sometimes, elements of the interaction have an impact on whether or not the individual buys. This paper examines defection before a customer becomes a customer. Reducing the incidence of almost customer episodes represents an opportunity for firms to optimize growth and profitability.

Examines the nature of meaningful customer relationships to determine what contributes to meaningfulness and to explore ways in which companies can establish more meaningful relationships with customers. Explores and applies the social psychology roots of the concept of meaning in a customer relationships context. Gleans evidence of meaningful customer relationships from the consumer psychology and marketing literature and from research conducted by the author. Examines situations where a company or a brand clearly occupies an important place in the life of a customer and discusses the characteristics of such relationships. Examines the factors that contribute to meaningful customer relationships. Looks at the implications for further customer research and for marketing and brand managers.

The Internet revolution is challenging marketers to attract and retain customers, who in many cases, migrate to the Web for speed and convenience. This appears to contradict the essence of true relationship marketing which is founded on the emotional dimensions of interpersonal relationships: trust, commitment, investment by individuals, dependence, two-way communications, a sense of attachment, reciprocity, shared benefits and mutuality. The authors analyse recent research into the profiles of Internet users and their expectations when entering into technology-based relationships. Suggestions are presented for those wishing to establish genuine relationships with Internet customers. Such an approach should mitigate the risk to organisations of becoming a commodity and being taken for granted by consumers, thereby precluding the creation of true customer value.

Relationship marketing has been embraced in a wide range of industries, including financial services. Despite considerable study and widespread application, it appears that many services marketers have accepted the concept of relationship marketing with little examination of the basis for genuine, quality relationships. Based on a review of the social psychology and relationship marketing literature, the authors offer a consumer‐focused approach to defining the principles of relationship marketing, and examine the conditions under which services marketers can expect to form relationships with their customers. Also presented are empirical findings on the predictors of the level of equity which resides in relationships between financial services providers and their retail customers. The research reveals that the affective dimensions of the service encounter best predict quality relationships. The implications for financial services marketers are discussed.

This paper examines four perspectives of relationshipmarketing that have been discussed in the marketing literaturein recent years and which are being touted as sources of long-termprofitability for organizations. We examine each of the fourperspectives (’’locking in‘‘ customers, customer retention, databasemarketing, and building strong, close, positive relationships)to assess their potential for achieving a sustained competitiveadvantage. Our analysis suggests that only those organizationsthat build strong, close, positive relationships with their customershave the potential to develop a sustained competitive advantagethat may lead to above normal performance.

This article presents the results of the analysis of data collected in a telephone survey of retail customers of banks and other financial institutions. The objective of the research is to identify various dimensions of the customers' relationships with their principal financial institution and to ascertain the factors that contribute to the types of close relationships that are likely to lead to customer retention, referrals, and long-term profitability. A survey of 400 adult retail bank customers provided data for analysis. The results indicate that the factors that contribute most to the establishment of close, satisfying customer relationships are affective variables, rather than situational or behavioral variables. The results also point to the existence of quite different segments of the retail bank market as defined by the type of relationship the customer wishes to have with his or her main bank. © 1997 John Wiley & Sons, Inc.. Inc.

The concept of the customer experience has entered the marketing lexicon in recent years and has now been accepted by many executives as an integral component of the firm’s value proposition. There is widespread acceptance also of the fact that solid technical performance of the conventionally defined components of the marketing mix is no longer sufficient to ensure long-term customer loyalty and that creating a positive customer experience leads to high levels of customer satisfaction and is an important step towards the establishment of customer relationships and lasting customer loyalty (Mascarenhas et al. 2006). This paper argues that the important concept of the customer experience is not sufficiently well understood, especially by retail executives, with the result that its potential is not fully realised. The paper draws on the results of proprietary qualitative research on retail shopping to illustrate the importance of gathering insight into the notion of the customer experience and into the context in which that experience is taking place if a retail firm or shopping centre is to create an experience that is meaningful to its customers.

In today's marketplace, the customer is presented with a myriad of products and services of greater variety and value than ever before. As competition becomes more intense, product and service providers are increasingly turning towards “service” or “service quality” as a means of achieving competitive advantage. Even in industries such as telecommunications, where significant technological advances have characterized the industry, companies are realizing that the best product no longer guarantees an advantage over the competition. The key ingredient in the formulation of a competitive service strategy is the proper measurement of service quality dimensions, as defined by the customer, and the continual monitoring of company performance along those dimensions. This article describes the process of identifying service quality dimensions as applied in two telecommunications network providers, one in Canada and one in Ireland. Results are compared and contrasted between the two countries.

This chapter calls into question the use of the term relationship to describe the interaction between customers and service providers. It raises issues relating to situations where the customer would acknowledge that a relationship is in place with a service provider, suggesting that a genuine relationship does not exist unless the customer feels there is one. It questions whether various approaches to building repeat business are really creating relationships. The chapter also explores in depth the concept of closeness in customer relationships, and presents empirical data to support the view that some relationships are closer than others. It also indicates that relationship closeness is an excellent predictor of customer satisfaction, share of the customer’s business, likelihood of customer retention, and referral behavior. Various conclusions and implications are explored, including the effect of increased reliance on technology on the ability of marketers to get close to their customers.

The marketing research industry in Canada has grown rapidly during the past twenty years or so, both in the number of users of research and the number of practitioners offering professional marketing research services, and in the type of research being done. The changing nature of the Canadian market-place, coupled with a growing appreciation of the cultural diversity of the country and of the fact that Canadian consumers are not exactly like Americans, has contributed to m increasing acceptance of marketing research in Canadian business. In addition, the use of research techniques in public sector and not- for-profit organisations has become generally accepted in recent years. The techniques used in Canadian marketing research have also undergone considerable change, as researchers are now making much greater use of recently-available technology, computer-based simulations, and automated data capture at the check-outs of retail stores. Possibly the greatest change has been in the increased use of qualita...

Proposes that the main objective here is a system being developed for segmenting industrial markets on the basis of the level demonstrated by buying centre members. Examines the factors which influence the individual member of the buying centre in the context of his/her participating in the acquisition of an innovation. Explores the concept of consumer creativity or maturity as developed in the context of consumer marketing, and considers factors which are deemed influential. Posits that greater success rates in new product development would be achieved if research and development worked in tandem with an identified cross‐section of sophisticated buying centre members.

This paper presents a profile of the consumerist and tests for significant differences between the consumerist and the average consumer. The findings suggest that the consumerist differs significantly on socioeconomic, life style, attitudinal, readership, and listenership variables, while constituting a sizeable segment (15 percent) of the population.