Innovation, urgency and acceptance at the 9th Vaccine Renaissance

Ebola, Measles, Malaria, and - oh my! - Zika were on the global agenda when the 9^th Vaccine Renaissance conference was convened in November of 2015. In fact, both vaccines and emerging infectious diseases were front and center in media reports at the time. Measles had re-emerged as a significant threat to children living in the United States earlier that year due to an outbreak linked to Disneyland theme parks¹, and reports of fetal malformations and other effects of the Zika virus were emerging from Brazil.^2,3 Vaccine researchers and public health advocates participating in this annual event were once again reminded of the importance of vaccine discovery, delivery, and – perhaps most important – vaccine acceptance, to prevent human morbidity and mortality worldwide.

The Vaccine Renaissance is an intimate (100-person) gathering of local, national and international vaccine experts that takes place in Providence, RI, and is coordinated by the University of Rhode Island's Institute for Immunology and Informatics (iCubed). Several major themes emerged during the 9^th convening, each of which is addressed in the compendium of reports in this issue of Human Vaccines & Immunotherapeutics. As summarized below, some of these important themes include: (1) the critical role of basic research innovations for vaccine development, (2) barriers that impede the urgent development of vaccines for emerging infectious disease threats, and (3) the importance of vaccine acceptance, at the population level, in the prevention of emerging (and re-emerging) infectious diseases.

The important connection between innovation and vaccine discovery was accurately described by Christian P. Nixon (Lifespan, Providence, Rhode Island) (p 3189) and is illustrated in his article in this issue of HV&I.⁴ He detailed the dynamics of malaria gametocyte structure and blood circulation, and posited that the distinct structural morphology of gametocytes is critical to their survival. Immune responses (and vaccines) that target structural antigens in gametocytes could make it more difficult for malaria to infect mosquitoes, leading to new gametocyte-blocking vaccines. Dr. Manobu Ato of the National Institute of Infectious Diseases in Japan described an equally exciting innovation: the development of a new mouse model for vaccine efficacy testing. At the 9^th Vaccine Renaissance, Dr. Ato described as yet unpublished studies in which this mouse model was used to measure subtle improvements in vaccine immunogenicity by the removal of a single regulatory T cell epitope using protein engineering.⁵

The selection of the right formulation for vaccine delivery was also addressed during the Vaccine Renaissance, in talks by Mark Poznansky (Vaccine and Immunotherapy Center, Massachusetts General Hospital), and Nikolai Petrovsky (Vaxine, and Flinders Medical Center). Dr. Poznansky described a self-assembling vaccine platform⁶ and RNA replicons⁷ that have shown great promise (respectively) in pre-clinical studies and early clinical trials. Dr. Petrovsky contributed a report on the surprising efficacy of inulin (Advax) as a vehicle for delivery for influenza vaccines, which is included in this issue of HV&I.⁸ All 3 types of vaccine formulation are admirably suited to developing ‘vaccines on demand’, a topic that has been addressed in a previous Vaccine Renaissance compendium.⁹

Barriers to vaccine development for emerging infectious diseases were addressed by a number of speakers at the Vaccine Renaissance. Kim Kraynyak (Inovio, BlueBird, Pennsylvania) not only shared excellent clinical trial data on the Inovio HPV (DNA) vaccine, but also provided detailed information about the design and development of the Inovio Ebola vaccine. In addition, she addressed the challenges that arise in organizing a Phase III trial across continents. Barriers to development were further addressed in a passionate testimony on the irradiated sporozoite malaria vaccine by Dr. Steven Hoffman of Sanaria. He described a series of recent successful clinical trials¹⁰ and addressed participant questions about the scaleability of the irradiated sporozoite technology. He also reported that Sanaria's path to the clinic may include clinical trials of low dose live sporozoite challenge, followed by (anti-malarial) cure. Other speakers who discussed barriers to clinical development included Laura White (Global Vaccines Inc.), who described an alpha-virus vectored Dengue vaccine¹¹, and Manon Cox of Protein Sciences, who has successfully launched an FDA-approved baculovirus-expressed influenza vaccine that has been hampered by slow uptake at the national level, despite the fact that the egg-component-free vaccine has some significant advantages.¹²

Barriers to vaccine acceptance were discussed by local public health authorities (Allys Clyne, Rhode Island Department of Public Health), who reported on methods used by the state to improve uptake and acceptance of HPV vaccines in Rhode Island. The Rhode Island Department of Health has developed a number of successful strategies, including mandatory HPV vaccination at school entry, which are likely to contribute to the future eradication of HPV among teenagers in the state.¹³

In another landmark talk that should improve vaccine acceptance, Dr. S. Sohail Ahmed of Glaxo Smith Kline (formerly Novartis) (p 3196) described recent work by his group¹⁴ on the worrisome linkage between narcolepsy, a rare condition, and vaccination with certain A(H1N1)pdm09H1N1 vaccines during the H1N1 pandemic in 2009. The development of narcolepsy was correlated with an increased frequency of antibodies to hypocretin (HCRT) receptor 2 in sera from patients who developed the side effect. These antibodies were reactive to a sequence from influenza nucleoprotein, YDKEEIRRIWR, which was similar to a sequence from the first extracellular domain of HCRTr2, YDDEEFLRYLWR. Additionally, the connection between vaccination and narcolepsy was found to be associated with residual NP protein, rather than the characteristics of the adjuvants used with the vaccine. A review of these important findings, which should allay some concerns about links between adjuvants and adverse effects, is included in the current compendium.¹⁵

Finally, Janet McNicholl (CDC) (p 3202) reported on a combined approach to the prevention of HIV transmission that is gaining acceptance in the field. Her report is also included herein.¹⁶ She proposes that future studies should consider the option of combining vaccines with microbicides or pre-exposure prophylaxis (PrEP) with antiretroviral drugs, since each of these interventions may only partially prevent HIV-1 infection. Oral PrEP is now FDA approved for HIV-prevention in high risk groups, but partial adherence reduces efficacy. If combined as biomedical preventions, an HIV vaccine could provide protection when PrEP adherence is low and PrEP could prevent vaccine breakthroughs. Other types of PrEP or microbicides may also be partially protective.

In summary, the 9^th Vaccine Renaissance covered a broad range of subjects, from basic immunology, to murine models of vaccine efficacy, and included discussions of adverse effects and vaccine acceptance. Articles in the current issue of Human Vaccines and Immunotherapeutics attest to the breadth, urgency, and relevance of vaccine research in the present time.

Disclosure of potential conflicts of interest

The authors also acknowledge their affiliation with EpiVax, Inc., a vaccine design and development company located in Providence, Rhode Island. Both authors are salaried employees of EpiVax, Inc. and own stock in the company (ADG) and/or options (ADG and LM). The authors have made every effort to avoid any conflict of interest between the objectives of EpiVax and the information that is provided in this article.

Acknowledgment

The contribution of Pooja Hindocha to the careful review of this article is gratefully acknowledged.

Funding

The authors would like to acknowledge The National Institutes of Health Grant R13AI094946-05 support for the Vaccine Renaissance Conference Series.