Next-generation rotavirus vaccine developers meeting: Summary of a meeting sponsored by PATH and the bill &amp; melinda gates foundation (19–20 June 2019, Geneva)

Fix, Alan; Kirkwood, Carl D.; Steele, A. Duncan; Flores, Jorge

doi:10.1016/j.vaccine.2020.11.034

Cited by 12 publications

(17 citation statements)

References 51 publications

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“…); new vaccination formats (newborn doses, boosters, etc. ); new oral vaccines (human neonatal vaccine RV3-BB) [ 78 ]; and, finally, new types of injectable vaccines that, since they are introduced directly into the bloodstream, avoid the intestine and thus the risk of causing intussusception. However, since the first contact with infectious RV particles occurs at the mucosal level, it is important to acquire not only systemic but also mucosal immunity.…”

Section: Rv Vaccine Pipelinementioning

confidence: 99%

The Rotavirus Vaccine Landscape, an Update

et al. 2021

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Rotavirus is the leading cause of severe acute childhood gastroenteritis, responsible for more than 128,500 deaths per year, mainly in low-income countries. Although the mortality rate has dropped significantly since the introduction of the first vaccines around 2006, an estimated 83,158 deaths are still preventable. The two main vaccines currently deployed, Rotarix and RotaTeq, both live oral vaccines, have been shown to be less effective in developing countries. In addition, they have been associated with a slight risk of intussusception, and the need for cold chain maintenance limits the accessibility of these vaccines to certain areas, leaving 65% of children worldwide unvaccinated and therefore unprotected. Against this backdrop, here we review the main vaccines under development and the state of the art on potential alternatives.

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Section: Rv Vaccine Pipelinementioning

confidence: 99%

The Rotavirus Vaccine Landscape, an Update

et al. 2021

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“…Therefore, these data require further con rmation in larger prospective studies. Nevertheless, the results suggest that CHIMs utilizing approved oral rotavirus vaccines warrant further development, particularly in contexts where the standard immunogenicity measure RV-IgA may not be an appropriate outcome, such as with next-generation, non-replicating vaccines 19 .…”

Section: Discussionmentioning

confidence: 99%

“…VP6 is available for recognition only after successful infection of host intestinal cells leads to uncoating of the outer capsid layer to reveal VP6 and initiate viral replication 21 . Therefore, alternate assays are likely needed to adequately assess immune responses for next-generation, non-replicating vaccines that use antigens other than rotavirus VP6 19 . Rotarix shedding has been used in phase 1 and 2 trials of a P2-VP8* parenteral vaccine candidate to evaluate for induction of mucosal immunity 22,23 .…”

Section: Discussionmentioning

confidence: 99%

“…We previously attempted to consider dose 1 response by evaluation of post-dose 1 shedding, and reported that post-dose 1 shedding as a marker for successful vaccine take or post-dose 1 shedding followed by lack of shedding post-dose 2 was not associated with subsequent year 1 rotavirus diarrhea 19,26 . However, among infants with post-dose 1 shedding specimens available for analysis (N = 176), 73% had specimens collected within 2 days following vaccination, meaning many detections at this time point could re ect passage of vaccine inoculum and not shedding indicative of viral replication, confounding interpretation of results relying on post-dose 1 shedding as a marker for successful vaccine take.…”

Section: Discussionmentioning

confidence: 99%

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Oral Rotavirus Vaccine Shedding as a Marker of Mucosal Immunity

Lee

Kader

Colgate

et al. 2021

Preprint

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Rotavirus remains a leading cause of pediatric diarrhea worldwide, in part due to underperformance of currently approved live-attenuated, oral vaccines in low-and-middle income countries (LMIC). Improved immune correlates of protection (CoP) for existing oral vaccines and novel strategies to evaluate the performance of next-generation vaccines are needed. Use of oral vaccines as challenge agents in controlled human infection models is a potential approach to CoP discovery that remains underexplored. In a live-attenuated, oral rotavirus vaccine (Rotarix, GlaxoSmithKline) efficacy trial conducted among infants in Dhaka, Bangladesh, we explored the potential for the second dose of the two-dose series to be considered a challenge agent through which rotavirus immunity could be explored, using fecal virus shedding post-dose 2 as a marker of mucosal immunity. Among 180 vaccinated infants who completed the parent study per protocol, the absence of fecal vaccine shedding following the second dose of Rotarix suggested intestinal mucosal immunity generated by the first dose and a decreased risk of rotavirus diarrhea through 2 years of life (RR 0.616, 95% CI 0.392-0.968). Further development of controlled human infection models for rotavirus, especially in prospective studies with larger sample sizes, may be a promising tool to assess rotavirus vaccine efficacy and CoPs.

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“…EED) that prevent successful take of live-attenuated vaccines in the gut, hopefully leading to improved efficacy; reduced cold-chain footprint and cost; opportunity via sequential scheduling strategies (e.g., "primeboost") to augment (rather than replace) current ORV programs; and development of combination vaccines to facilitate administration and improve access. A meeting of NRRV vaccine developers was organized by PATH and held in Geneva, Switzerland in June 2019; additional information regarding the following vaccine candidates are available in the meeting proceedings 145 . An overview of NRRV candidates currently in development is provided in Table 3.…”

Section: Non-replicating Rotavirus Vaccines (Nrrvs)mentioning

confidence: 99%

Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines

Lee

2020

Human Vaccines & Immunotherapeutics

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In the decade since oral rotavirus vaccines (ORV) were recommended by the World Health Organization for universal inclusion in all national immunization programs, significant yet incomplete progress has been made toward reducing the burden of rotavirus in low- to middle-income countries (LMIC). ORVs continue to demonstrate effectiveness and impact in LMIC, yet numerous factors hinder optimal performance and evaluation of these vaccines. This review will provide an update on ORV performance in LMIC, the increasing body of literature regarding factors that affect ORV response, and the status of newer and next-generation rotavirus vaccines as of early 2020. Fully closing the gap in rotavirus prevention between LMIC and high-income countries will likely require a multifaceted approach accounting for biological and methodological challenges and evaluation and roll-out of newer and next-generation vaccines.

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Next-generation rotavirus vaccine developers meeting: Summary of a meeting sponsored by PATH and the bill & melinda gates foundation (19–20 June 2019, Geneva)

Cited by 12 publications

References 51 publications

The Rotavirus Vaccine Landscape, an Update

The Rotavirus Vaccine Landscape, an Update

Oral Rotavirus Vaccine Shedding as a Marker of Mucosal Immunity

Update on rotavirus vaccine underperformance in low- to middle-income countries and next-generation vaccines

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