Research on Universal Vaccine for Influenza Uncovers More Than Just Financial Limitations

A recent review article published in Vaccine on the status of influenza vaccines, their short-comings, and ways to improve them suggests the potential for significant improvements in the performance of future influenza vaccines. The review focuses on several key aspects of influenza virus biology pertaining to traditional and new approaches to vaccine production.

In the review, author Francesco Berlanda Scorza, PhD, the Scientific Director of the Influenza Vaccine Project, Program for Appropriate Technology in Health (PATH), describes the currently licensed influenza vaccines and their limitations, general approaches for low- and middle-income country markets, technical and regulatory assessment, and the status of influenza vaccine research and development activities.

In the discussion regarding short-comings associated with the currently licensed influenza vaccines, Scorza et al note past examples of vaccine mismatch with seasonal influenza strains, as well as the underlying causes of such mismatches. In one instance, the World Health Organization (WHO) prediction of the circulating strain was actually correct, however, a mutation occurred in the egg-adapted seed virus sent to vaccine manufacturers. The reasons for the limited effectiveness of the vaccine against influenza A (H1N1) pdm09 in children during the 2013/2014 influenza season remain to be fully elucidated, but the situation in general highlights, "... the unpredictability of seasonal influenza epidemics and the challenge for current-generation vaccines that can only follow changes in circulating viruses." Dr. Scorza and his colleagues suggest that such uncertainty may be overcome through the development and application of universal influenza vaccines with the potential to induce a more broad form of protective immunity. Ideally, such vaccines would provide combined protection from antigenic drift and shift, and perhaps even confer lifelong immunity.

Another important topic covered in the review is the disparity of effective influenza vaccine availability outside of the developed world and the challenges this presents with regard to pandemic outbreaks. In reference to this disparity, Scorza and colleagues state that, "Despite sufficient influenza vaccine production capacity for annual needs in high-resource countries, influenza vaccination coverage rates among high-risk groups are below the targets set by national governments and recommended by WHO in these settings."

The majority of the information presented in the review pertains to a large number of influenza vaccines in development and the mechanisms by which vaccines can be improved based on an evolving understanding of the virus and how to target it. According to Scorza et al, "Vaccine candidates currently in the development pipeline can be divided into the following general categories: (1) those designed to elicit antibody responses to structurally conserved regions of HA [hemagglutinin] and surface exposed membrane matrix protein (M2e), and (2) those that induce cross-protective T-cell responses against internal proteins like NP [nucleoprotein] and M1 [matrix protein 1]." More simply put, the immunogens in the first category would prevent infection and those in the second category would reduce disease severity.

Scorza et al also point out that, "While the influenza field has seen substantial investment over the last ten years, the majority of funding has focused on ensuring the sustainability of manufacturing within high resource settings and broadening manufacturing options so that influenza vaccines are not solely dependent on egg-based production." Although this approach may have its merits, the development of novel approaches to immunogen design has become a popular new strategy. Some of the new technologies currently in development to improve vaccine production include, "... faster generation of reassortant seed viruses, improved manufacturing consistency and yield, use of cell culture instead of eggs, improved adjuvants, quadrivalent vaccines, and prime-boost strategies." Adjuvants in particular have been moderately effective in increasing cross-reactivity against viral strains not included in the vaccine.

Beyond the information presented in the review, Scorza et al describe the challenges involved in the development of universal influenza vaccines, stating, "No consensus has been achieved on what primary clinical endpoint universal influenza vaccines should achieve to be considered successful. Whether or not they should completely prevent influenza infection or reduce the severity of disease is still being debated."

William Perlman, PhD, CMPP is a former research scientist currently working as a medical/scientific content development specialist. He earned his BA in Psychology from Johns Hopkins University, his PhD in Neuroscience at UCLA, and completed three years of postdoctoral fellowship in the Neuropathology Section of the Clinical Brain Disorders Branch of the National Institute of Mental Health.