Clinical Trial: Yellow Fever Vaccine on Statin/ Non Statin Subjects

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Using Systems Vaccinology to Elucidate the Effects of Anti-inflammatory Therapy on Immune Response After Vaccination With a Live Attenuated Vaccine

Brief Summary: Since the 1st pandemic of the 21st century caused by SARS coronavirus, the world has experienced outbreaks of swine origin H1N1 influenza, Ebola and Zika viruses, which have all resulted in global health crises. Rapid mass vaccination with an effective vaccine such as a live attenuated vaccine, of vulnerable immune-naïve populations to establish herd immunity is an approach to control outbreaks. Such live attenuated vaccine had been used with great success in sporadic yellow fever outbreaks and recently successfully employed in Ebola field trial, both of these diseases have the potential for pandemic spread. Indeed, live attenuated vaccines have proven especially effective in controlling childhood diseases and have even succeeded in eradicating polio and measles from most parts of the world. However, deployment of such vaccines for pandemic control cannot be limited to children but must include adults in order to rapidly elevate herd immunity rates to halt transmission. Vaccinating adults may produce efficacy rates significantly different to those observed in children due to the prevalence of chronic diseases and their associated metabolic complications. Presently, there are 1 billion people who are overweight, many suffer from concurrent metabolic disorders. As activation of the adaptive immunity is reliant on a robust innate immune response to vaccines, metabolic disorders and long-term anti-inflammatory therapy with interventions such as statins may reduce vaccine immunogenicity resulting in suboptimal efficacy in this subpopulation. This study would therefore test the hypothesis that statins reduce live attenuated vaccine immunogenicity. We will combine a clinical trial with systems vaccinology approaches to define the impact statins has on the innate immune, B and T-cell responses to live attenuated vaccination. Our study will thus extend upon another recently completed trial by us and will provide new insights into the determinants of vaccine efficacy in

Detailed Summary:

Despite successful control of many infectious diseases since the 19th century, viral diseases remain an important and significant health burden in the 21st century. In fact, the turn of the 21st century saw the emergence of not only new but also re-emergent pathogens such as SARS, MERS, West Nile, Ebola, dengue and Zika viruses. In addition, the modern world is highly mobile and interconnected. The spread of infectious diseases is imminently only a flight away. It is thus of no surprise that epidemics in this century are happening at a much faster pace and spreading quicker to cause disruption to human health, society and the economy. Vaccination, particularly with a live attenuated vaccine (LAV), which has the most successful track record among the various forms of vaccines, remains the most economical public health tool available to prevent or stop the spread of infections and alleviate human sufferings. Rapid mass vaccination of at risk populations to establish herd immunity has been successfully employed to control sporadic YF outbreaks in Africa and South America. More recently, a clinical trial showed that ring vaccination of contacts with Ebola patients completely abrogated secondary virus spread. Vaccination in times of pandemics, however, cannot be limited to children but must include adults in order to rapidly elevate herd immunity rates to halt further transmission.

The use of LAV in adults has several important challenges that have not been systematically addressed. The population demographics in Singapore, like most developed countries have changed drastically over the past 3 decades. Along with improved nutrition, populations are now living longer but with increasing prevalence of chronic diseases such as obesity and dyslipidemia. Consequently, the anti-cholesterol group of drugs, with pleiotropic properties, statins, are among the commonest drugs prescribed
Sponsor: Singapore General Hospital

Current Primary Outcome: the adaptive immune response to YF vaccination in (A): Adult human volunteers who are on long term statins therapy and (B): Adult human volunteers (controls) [ Time Frame: 28 days ]

the difference in neutralizing antibody titer to YF17D at Day 28, as measured by plaque reduction neutralization test (PRNT)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • the difference in innate immune response to YF vaccination in adult human volunteers on long term statins therapy compared to controls post-YF vaccination [ Time Frame: 28 days ]
    viremia levels response in adult human volunteers on long term statins therapy compared to controls post-YF vaccination
  • the cellular immune response of adult human volunteers on long term statins therapy with controls following YF vaccination. [ Time Frame: 28 days ]
    To examine the Cd4+ and Cd8+ T cell response in adult human volunteers on long term statins therapy compared to controls post-YF vaccination


Original Secondary Outcome: Same as current

Information By: Singapore General Hospital

Dates:
Date Received: March 13, 2017
Date Started: March 8, 2017
Date Completion: January 31, 2020
Last Updated: April 11, 2017
Last Verified: April 2017