Expert Review of Vaccines 10-year anniversary issue

From its launch in 2002, Expert Review of Vaccines has provided a unique forum for discussion and review of vaccine-related topics by a wide range of vaccine scientists and key opinion leaders and we hope that this journal has made, and will continue to make, its own small but important contribution to the field of vaccinology. In the first issue of the journal, in an editorial article titled, ‘Is there a future for vaccines’, Robert Goldberg outlined his perspective on the role that government, public and private research looked set to play in vaccinology [1]. He called for “market forces to capitalize (figuratively and literally) on the potential of vaccine research” and warned of the danger of vaccinology and development descending into the “brackish backwater of other biotechnology and pharmaceutical enterprises”. There is plenty of evidence that there was a robust response to Goldberg’s call with the global market penetration of a number of major new vaccines into national schedules in the past decade (including pneumococcal, meningococal, rotavirus and human papillomavirus vaccines), leading to recognition by the major pharmaceutical companies that investment in vaccines could provide a substantial and secure financial return. This forthright perspective immediately sparked the attention of R Rao Koganty who argued that, while cancer, Alzheimer’s and AIDS could be research opportunities for private enterprises, epidemics should not be a market opportunity but should remain the responsibility of government-supported agencies [2]. He also went on to note that “the so-called ‘third world diseases’ may never attract the efforts of profit-oriented multinational corporations”. Given the global roll out – using novel financing mechanisms – of pneumococcal, Haemophilus influenzae type b (Hib) and rotavirus vaccines that is now underway, the programs on neglected tropical diseases (which include major donations of drugs by industry) and the African Meningitis Vaccine Project, we can enthusiastically report that this was one perspective that was thankfully derailed.

Today, as we celebrate 10 years since the launch of Expert Review of Vaccines, we can look back over these perspectives, and those raised by others in both the inaugural issue and this anniversary issue, as a marker of how far we have come in the last decade and how much further we have yet to go.

In 2002, in the 5-year view of his special report article, Matthius von Herrath noted that, “In diabetes, one could envision a combination of anti-CD3 treatments with an islet antigen-specific DNA vaccine” [3]. Currently, teplizumab, an anti-CD3 humanized Fc-engineered monoclonal antibody, is now in Phase III trials for the treatment of Type 1 diabetes mellitus [101]. Furthermore, despite some disappointing European Phase III trials, research into Diamyd^®, a vaccine designed to induce tolerance to a major autoantigen in Type 1 diabetes, the 65-kDa isoform of the recombinant human glutamic acid decarboxylase protein (GAD65), continues and researchers remain hopeful of its potential to protect against disease development in high-risk individuals [102].

In the inaugural issue, we (Bethell and Pollard [4]) predicted that following the success of the monovalent serogroup C meningococcal (MenC) conjugate vaccine, quadrivalent ACYW meningococcal conjugate (MenACYW) vaccines would be licensed but little used, except for high-risk groups, because of the low rates of disease caused by meningococcal serogroups other than B and C in most developed countries, unless epidemiology were to change. This projection has been proven largely correct in Europe thus far, but despite historically low rates of meningococcal disease in the USA, the vaccine is administered in that country in a two-dose schedule for adolescents, and has been shown to be effective. We also wrongly predicted the successful development of combination pneumococcal–meningococcal conjugate vaccines, for which acceptable immunogenicity has yet to be shown, although other combination vaccines with Hib (such as Hib–MenC) have been deployed, and we correctly highlighted the successful development of the African serogroup A meningocccal vaccine. Serogroup B remains the major challenge for control of meningococcal disease but today there is one vaccine being reviewed for licensure by the European regulator and another advancing through clinical development. In 2002, we said that “the serogroup B vaccine that eventually becomes routinely used will likely contain several recombinant OMPs and possibly LPS epitopes…”. Watch this space to see if we were right.

The 2009 H1N1 pandemic followed a special focus issue by the journal on influenza vaccines [103] and reinvigorated both research and public perception of influenza vaccines and vaccine safety profiles. The concerns raised by Kogany on the importance of pandemic vaccine responses remaining in government-supported agencies [2] have been echoed by some concerned about conflict of interest in the WHO [5]. While discussion on topics such as this should of course not be suppressed, the availability and safety profile of the pandemic H1N1 vaccine helped to bring a prompt end to circulation of this strain in high-risk groups and is testament to developments and advances in influenza vaccine research. However, the reported link with narcolepsy may hold up development of adjuvanted influenza vaccines until the phenomenon is fully understood [104]. The greatest risk from the pandemic today may be the lingering perception that the event was overstated or that the vaccines were unsafe or ineffective, leading to a complacency that could be a threat to us all when the next pandemic comes.

The inaugural issue of Expert Review of Vaccines touched briefly on the clinical trials of virus-like particle vaccines against human papillomavirus (HPV) [6]. The HPV vaccines have consequently become one of the runaway success stories of the past decade and in this issue, Nobel Laureate Harald zur Hausen discusses how he arrived at this hypothesis and his predictions on the impact we can expect to see on cervical cancer rates in the coming decade [7].

This anniversary issue reflects on developments in the past decade and developments yet to come for a wide range of diseases and indications. Featured are the following articles:

• • The Decade of Vaccines Collaboration: developing a global vaccine action plan (Elias) [8];

• • Pertussis vaccines: where to now? (Poolman et al.) [9];

• • HPV vaccines: what remains to be done? (zur Hausen) [7];

• • A universal influenza vaccine: the BiondVax story – (Ben-Yedidia and Rudolph) [10];

• • Improving immunogenicity and efficacy of influenza vaccine in older adults (Cao et al.) [11];

• • Adenovirus-vectored drug–vaccine duo as a potential driver for conferring mass protection against infectious diseases (Zhang et al.) [12];

• • Heat shock proteins and cancer vaccines: developments in the past decade and chaperoning in the decade to come (Murshid et al.) [13];

• • Developments in virus-like particle-based vaccines for infectious diseases and cancer (Buonaguro et al.) [14];

• • Chlamydia vaccines: recent developments and the role of adjuvants in future formulations (Igietseme et al.) [15];

• • From brain passage to cell adaptation: the road of human rabies vaccine development (Wu et al.) [16];

• • Vaccination of travelers: how far have we come and where are we going? (Chen et al.) [17];

• • Glycoconjugate vaccines and immune interactions, and implications for vaccination schedules (Borrow et al.) [18].

Also featured are two drug profile articles outlining the progress in the development of two influenza vaccines:

• • The seasonal influenza vaccine Agriflu^® (Vajo) [19];

• • MF59™-adjuvanted seasonal influenza vaccine in young children (Puig-Barberà et al.) [20].

As Rino Rappuoli, editorial board member and frequent author for the journal recently contemplated, licensing of a new vaccine can require approximately 80,000 people in clinical trials [21]. Furthermore, if all Phase I–III studies are performed sequentially, vaccines entering Phase I studies require approximately 10 years for clinical testing. The development of recombinant DNA technology along with high-throughput methods of identification, has undoubtedly changed vaccine discovery and shortened the time required for vaccine development. However, in order to further shorten this development time, systems biology may provide a new approach to interrogate the mechanisms of vaccine-induced immunity in humans. For example, Querec et al. were able to identify and then validate early gene signatures that predicted immune responses to a yellow fever vaccine [22]. Such approaches could be used to improve vaccine design, identify correlates of protection and might provide new insights into the action of adjuvants and lead to smart vaccine design.

How fitting that our journal’s first decade should end with the launch of the ‘Decade of Vaccines’ which will take Expert Review of Vaccines through adolescence. This issue features an editorial article on the Decade of Vaccines collaboration [9]. Led by an international steering committee, this aims, among other things, to help create the right market incentives to ensure an adequate and reliable supply of affordable vaccines and to expand public demand and political commitment for the use and financing of immunization services [9]. This Decade of Vaccines was called for in January 2010 at the World Economic Forum, by Bill and Melinda Gates as they announced a pledge from their foundation to commit US$10 billion over the next decade to help research, develop and deliver vaccines for the world’s poorest countries. While, as Kogany noted, the efforts of profit-oriented corporations may not be directed to aid vaccine development and distribution in the world’s poorest countries, in the next decade we can remain hopeful that efforts such as the Decade of Vaccines collaboration will go some way to redress the imbalance in access to safe, effective vaccines seen worldwide.

Financial & competing interests disclosure

Andrew J Pollard does not receive any personal payments from vaccine manufacturers nor other forms of personal support. He conducts clinical trials on behalf of Oxford University, which are sponsored by vaccine manufacturers and his institution receives unrestricted educational grants from vaccine manufacturers for educational meetings. Lauren Constable is a full-time employee of Expert Reviews Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.