The New Generation of Vaccine Development for RSV

This year, the theme for World Immunization Week is “Protected Together, #VaccinesWork.” This theme brings to heart and mind the significant efforts of those who have developed life-saving vaccinations for millions of people across the globe. It also highlights the potential for a great improvement in rates of those diseases for which vaccines are not yet available.

Respiratory Syncytial Virus (RSV) is the largest, most significant respiratory disease in children and the elderly for which a successful vaccine has not yet been developed. According to the Centers for Disease Control and Prevention, an average of 2.1 million outpatient visits and more than 57,000 hospitalizations among children under the age of five occur each year in the United States. Among the elderly, the virus is equally concerning with over 177,000 hospitalizations and 14,000 deaths among adults older than 65 each year.¹

Researchers from the industry and academia have struggled for decades to get an RSV vaccine to the patients who need it. The virus was first identified over 60 years ago, in 1957.² In the late 1960’s, infants and young children who received formalin-inactivated RSV developed moderately high levels of serum antibodies, but did not develop resistance to infection. Sometime later, some infants vaccinated with this initial formulation developed a more serious disease and two infants died. The trials were ended and work to develop an RSV vaccine stopped for several years.³

Few advancements in the field occurred during the 1980s and 1990s. In the early 2000s, Wyeth (now Pfizer) and Sanofi tested subunit vaccines with purified F protein via maternal immunization and the RSV fusion attachment and matrix proteins in the elderly, respectively.² Since then, there is a renewed effort to address this serious condition. Today, there are more than 100 RSV clinical trial studies currently taking place globally.⁴ New RSV vaccines currently being developed and moved into clinical trials by many companies including Bavarian Nordic, GlaxoSmithKline, Merck, Novovax, Takeda, VaxArt, and others.

Challenges to RSV Vaccine Development
Safety concerns following the trial in the 1960s likely had the biggest impact on progress toward developing a new RSV candidate. Determining the probable cause of the infant deaths- formalin fixation of RSV- took years. The specific contribution of the fixation step took additional time to determine.

The lack of a suitable small animal models for RSV vaccine development that could fully mimic human infection and disease also delayed studies on pathogenesis. More than 30 years after the human clinical trial, researchers identified a large animal model (the cynomolgus macaque) in which they were able to duplicate the hypersensitivity response found in humans.⁵

As subunit vaccines were just coming into development during the 1980s, and the technology to develop and produce the immunogenic subunits of RSV took time, the time to evaluate new generations of RSV vaccines was delayed for many years. Finally, only recently have renewed investigations of potential adjuvants for RSV begun.

Need for innovation and expertise
Companies seeking to develop solutions in this next generation of RSV vaccines require specialized services to support their clinical trials. For example, IQVIA Laboratories is currently working with a large vaccine manufacturer to develop and validate new immunogenicity platforms to enhance the robustness of their immunogenicity data supporting their RSV vaccine trial.

Any sponsor seeking external laboratory services for development of an RSV vaccine should ensure the partner has the necessary technology and expert scientists to conduct appropriate efficacy monitoring during the study. Immunogenicity testing using enzyme-linked immunosorbent assays (ELISA) and functional assays by viral neutralization are offerings with which the partner should be able to show competence and confidence. IQVIA Laboratories is currently in discussions with partner companies around prototype assays that can be used for RSV vaccine development. We have partnered with both large and small pharmaceutical companies to develop traditional neutralization assays including a plaque reduction neutralization test (PRNT) for early phase vaccine development. To date, regulatory bodies have relied on the traditional neutralization methods to support vaccine immunogenicity studies; however, IQVIA Laboratories has worked with our pharmaceutical partners with newer technologies to enhance throughput and lower subjectivity of RSV neutralization, such as fluorescent plaque readout methods and reporter virus particles (RVP).

With the expertise and input from the right laboratory partner, sponsors can make great progress toward the development of important vaccines.

Another piece in the prevention puzzle
As our technology improves and our knowledge increases, we have been able to overcome some of the fears generated from the early attempts to develop a vaccine for RSV. World Immunization Week offers an opportunity for us all to focus on one of the greatest benefits to public health that has ever been developed. As we continue to work to add conditions such as RSV to the list of those that are vaccine-treatable, we will indeed see that we can be “Protected Together.”

References:

1. https://www.cdc.gov/rsv/research/us-surveillance.html
2. http://www.ncbi.nlm.nih.gov/pubmed/13478579?dopt=Abstract
3. http://novavax.com/download/files/pipeline/RSV_Vaccine_Timeline_FINAL.pdf
4. https://clinicaltrials.gov/ct2/results?cond=RSV+Infection&term=&cntry=&state=&city=&dist=
5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC136757/