Japanese encephalitis virus is a mosquito-borne member of the Flaviviridae family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality, and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for the spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO^®) has been approved by the US Food and Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of the introduction of JEV into the US, the need to integrate planning for such an event in public health policy, and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.

The recombinant vesicular stomatitis virus-Zaire Ebolavirus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP) was highly effective against Ebola virus disease in a ring vaccination trial conducted during the 2014–2016 outbreak in Guinea and is licensed by regulatory agencies including US FDA, EMA, and prequalified by WHO. Vaccination studies in a nonhuman primate (NHP) model guided initial dose selection for clinical trial evaluation. We summarize two dose-ranging studies with the clinical-grade rVSVΔG-ZEBOV-GP vaccine candidate to assess the impact of dose level on immune responses and efficacy in an NHP Ebola virus (EBOV) challenge model. Forty-six cynomolgus macaques were vaccinated with a wide range of rVSVΔG-ZEBOV-GP doses and challenged 42 days later intramuscularly with 1000 pfu EBOV. Vaccination with rVSVΔG-ZEBOV-GP induced relatively high levels of EBOV-specific IgG and neutralizing antibodies, measured using the same validated assays as used in rVSVΔG-ZEBOV-GP clinical trials. Similar responses were observed across dose groups from 1 × 10⁸ to 1 × 10² pfu. A single vaccination conferred 98% protection from lethal intramuscular EBOV challenge across all dose groups. These results demonstrate that robust antibody titers are induced in NHPs across a wide range of rVSVΔG-ZEBOV-GP vaccine doses, correlating with high levels of protection against death from EBOV challenge.

Nipah virus (NiV) is a deadly zoonotic disease with pandemic potential, prioritized by the World Health Organization for research and vaccine development. Since Bangladesh has faced annual NiV outbreaks and repeated spillovers since 2001, it is likely to be the site of a Phase II vaccine trial. This study explored people's knowledge about NiV and their willingness to participate in a NiV vaccine trial in Bangladesh. We conducted a mixed methods study, collecting qualitative and quantitative data from Mirpur township, Dhaka, and NiV-affected Faridpur District. From December 2021 to November 2022, the team interviewed adult male and female respondents responsible for household treatment and vaccination decisions. The team conducted 66 in-depth interviews and 978 survey interviews. Many in-depth interviewees were aware of NiV and, when asked if they would participate in a NiV vaccine trial, responded with one of three options: willing, unwilling, or would decide later. They were concerned about vaccine safety and side effects when making a decision about participation. In the survey, more respondents from Mirpur township, Dhaka, had heard about a disease transmitted from bats to people (57 %, 272/478 vs. 52 %, 262/500) and were willing to participate in a vaccine trial (45 %, 217/478 vs. 22 %, 111/500) than those from Faridpur. A high number expressed willingness to take an investigational NiV vaccine during an outbreak (Dhaka 75 %, 205/272 vs. Faridpur 81 %, 398/491 Faridpur). We did not find any association between knowledge about NiV and willingness to participate in a NiV vaccine trial. Many respondents expressed willingness to participate in a NiV vaccine trial, especially during an outbreak, suggesting that such a trial may be feasible in Bangladesh. Given concerns about safety and side effects, clear communication on these issues may support informed participation.

Clinical trials conducted in low resource settings of vaccines against unlikely pandemics generate practical barriers to achieving genuine informed consent. Uncertainty over the likelihood of the occurrence of emerging disease threats complicates risk-benefit considerations. We explored how people interpreted the language of a draft consent form for a Phase II trial of a vaccine against Nipah virus (NiV), a lethal bat-borne zoonosis, and assessed their willingness to participate after learning about the trial procedures. We conducted a mixed-methods study collecting data from residents of Dhaka city, and Faridpur District between December 2021 and November 2022. Our qualitative team revised a draft consent form with input from the community, while the quantitative team conducted face-to-face interviews of 978 household heads making vaccine and treatment decisions. We presented the consent form to 20 respondents. They expressed a desire to learn more about NiV disease and sought clarification on the vaccine trial process, use of a placebo, privacy and confidentiality, potential side effects, and compensation procedures. During the quantitative survey, among 328 respondents who indicated a willingness to participate in the vaccine trial, only 1 % (3/328) were familiar with the concept of a placebo. After the quantitative data collection team explained the meaning of a placebo, 61 % (199/328) expressed their willingness to participate in the trial. Our data suggest that obtaining informed consent for vaccine trials against pathogen with pandemic potentials is feasible but requires a commitment to eliciting study participants' perspectives and tailoring study materials to address their concerns and gaps in understanding.

Japanese encephalitis virus is a mosquito-borne member of the Flaviviridae family. JEV is the leading cause of viral encephalitis in Asia and is characterized by encephalitis, high lethality and neurological sequelae in survivors. The virus also causes severe disease in swine, which are an amplifying host in the transmission cycle, and in horses. US agricultural authorities have recently recognized the threat to the swine industry and initiated preparedness activities. Other mosquito-borne viruses exotic to the Western Hemisphere have been introduced and established in in recent years, including West Nile, Zika, and chikungunya viruses, and JEV has recently invaded continental Australia for the first time. These events amply illustrate the potential threat of JEV to US health security. Susceptible indigenous mosquito vectors, birds, feral and domestic pigs, and possibly bats, constitute the receptive ecological ingredients for spread of JEV in the US. Fortunately, unlike the other virus invaders mentioned above, an inactivated whole virus JE vaccine (IXIARO®) has been approved by the US Food & Drug Administration for human use in advance of a public health emergency, but there is no veterinary vaccine. This paper describes the risks and potential consequences of introduction of JEV in the US, the need to integrate planning for such an event in public health policy and the requirement for additional countermeasures, including antiviral drugs and an improved single dose vaccine that elicits durable immunity in both humans and livestock.