Vaccine and Virus Science

Oral live attenuated polio vaccine (OPV) and inactivated polio vaccine (IPV)are powerful but imperfect tools.Establishing and maintaining global polio eradication requires carefully considering how best to use both. OPV has been the primary tool for producing herd immunity because it is easy to administer, affordable, and produces excellent protection from infection in healthy people. However, it also has reduced efficacy in the most at-risk populations and can cause poliomyelitis either as a rare side effect of vaccination or by genetically reverting to a wild-like phenotype and circulating within the population. IPV has an excellent safety record, provides durable protection from paralysis with high efficacy, but is more expensive and more difficult to administer compared to OPV. It also produces little protection from infection when used by itself, without being combined with exposure to live poliovirus. Both vaccines require at least 3 doses to be maximally effective. Our research is focused on questions that will help further rationalize global polio vaccination policy to complete eradication and provide durable post-eradication protection.

INACTIVATED POLIO VACCINE (IPV)

  • Modelingan ImprovedIPV
  • IPV to AccelerateEradication

ORAL POLIO VACCINE (OPV)

  • Genetic Analysis of Sabin-like Viruses
  • OPV Transmissibility

INACTIVATED POLIO VACCINE (IPV)

Modeling IPV Clinical Trials

We are interested in modeling the effectiveness of improved IPV candidates. These candidate vaccines would have improved intestinal immunogenicity, and modeling could inform which candidates would have the most chances of passing Phase II clinical trials.

IPV to Accelerate Eradication

To mitigate the risks associated with the emergence of Vaccine-Derived Poliovirus (VDPV), the Global Polio Eradication Initiative plans to withdraw type 2 oral polio vaccine (OPV) from vaccination efforts in 2016. In order to mediate the resulting serotype 2 immunity gap, GPEI is working to introduce the inactivated poliovirus vaccine (IPV) in routine immunization across all countries. The impact of reduced intestinal immunity, a lower case-to-infection ratio, and possibly increased post-cessation outbreak risk posed by the IPV switch needs to be quantitatively understood. Using an individual-based polio transmission model, we aim to quantify the effectiveness of routine vaccination with IPV in preventing live poliovirus outbreaks, the impact of conducting IPV campaigns to respond to outbreaks, and the influence of IPV on the time it will take to detect the first cases of an outbreak. The model includes detailed intra-host dynamics based on a quantitative metastudy of the literature on the infection duration and immune response to an OPV challenge. For example, the immunity priming and boosting behaviors described by the model are consistent with recent clinical trial results. This work quantifies the association between outbreak risk and RI coverage, intestinal immunogenicity of IPV, the number of IPV doses used, the transmissibility of poliovirus in different settings, and the time interval between the seeding and detection of an outbreak.

ORAL POLIO VACCINE (OPV)

Genetic Analysis of Sabin-like Viruses

One issue of critical importance to completing polio eradication is eliminating circulating vaccine-derived poliovirus (cVDPV): wild-phenotype poliovirus outbreaks that result from inadequate population immunity and the genetic instability of live oral poliovirus (Sabin) vaccine. The processes responsible for genetic reversion of OPV in humans are incompletely understood because it has historically been difficult to gather and interpret data about Sabin virus evolution in the locations where cVDPV has occurred. We worked with partners at the Centers for Disease Control to perform an analysis that combined whole-genome sequencing of poliovirus isolates collected during routine surveillance in Nigeria with a sophisticated model of polio intra-host dynamics to provide quantitative insight into the genetic evoluation of polio vaccine in the field. Our observations reduce uncertainties around the timescales of genetic reversion that are a necessary component to more accurately model the process of cVDPV emergence and defining baselines for a potentially improved live vaccine.

OPV Transmissibility

Oral polio vaccine is transmissible from person to person. Vaccine transmission is both a "feature and a bug" of the live vaccine: it facilitates secondary immunization where a single vaccine dose can immunize more than one person, but coupled with a genetic instability it can lead to outbreaks of circulating vaccine-derived polio (cVDPV). These outbreaks can cause paralysis and pose a threat to the success of polio eradication. The magnitude of this secondary immunization and its transition from beneficial to dangerous have not been well-quantified. We are working to fill this gap by reviewing the transmission literature to quantify transmissibility in different settings and we are partnering the with Bill and Melinda Gates Foundation and other research groups to explore new transmission studies. Our primary objective is to produce a mechanistic model of OPV transmission that can be used to better understand the cVDPV risk and to quantify the impact of changing global vaccination policy.