Does Anybody Want an Injectable Rotavirus Vaccine, and Why? Understanding the Public Health Value Proposition of Next-Generation Rotavirus Vaccines

Abstract

Routine infant immunization with live, oral rotavirus vaccines (LORVs) has had a major impact on severe gastroenteritis disease. Nevertheless, in high morbidity and mortality settings rotavirus remains an important cause of disease, partly attributable to the sub-optimal clinical efficacy of LORVs in those settings. Regardless of the precise immunological mechanism(s) underlying the diminished efficacy, the introduction of injectable next-generation rotavirus vaccines (iNGRV), currently in clinical development, could offer a potent remedy. In addition to the potential for greater clinical efficacy, precisely how iNGRVs are delivered (multiple doses to young infants; alongside LORVs or as a booster; co-formulated with Diphtheria-Tetanus-Pertussis (DTP)-containing vaccines), their pricing, and their storage and cold chain characteristics could each have major implications on the resultant health outcomes, on cost-effectiveness as well as on product preferences by national stakeholders and healthcare providers. To better understand these implications, we critically assessed whether there is a compelling public health value proposition for iNGRVs based on potential (but still hypothetical) vaccine profiles. Our results suggest that the answer is highly dependent on the specific use cases and potential attributes of such novel vaccines. Notably, co-formulation of iNGRVs with similar or greater efficacy than LORVs with a DTP-containing vaccine, such as DTP-Hib-HepB, scored especially high on potential impact, cost-effectiveness, and strength of preference by national stakeholders and health care providers in lower and middle income countries.

What Drives the Value of a Shigella Vaccine?

“…Multiple valuable public health interventions, not all of which are vaccines, are thus coming at a time of increasingly crowded immunization schedules and finite resources. The need to prioritize among these has prompted calls for critical and systematic assessments of the full public health value of individual vaccine candidates while still in development [6,7]. "Full public health value" refers to the full health, economic, and societal value of a vaccine as seen by a broad range of stakeholders, including local and global perspectives, and aims to articulate both its direct (individual) and indirect (population) effects.…”

Novel mRNA-based VP8* vaccines against rotavirus are highly immunogenic in rodents

“…The reason for the modest vaccine efficacy and effectiveness in LMICs is likely multifactorial and may also be related to the lower immunogenicity and efficacy of other oral vaccines demonstrated in these settings 4,[7][8][9] . With the additional, if low, risk of vaccination-associated intussusception reported for two live-attenuated oral rotavirus vaccines in post-marketing studies in high-and middle-income countries 10,11 , there is growing interest in the development of non-replicating parenteral vaccines that might overcome the limitations of current rotavirus vaccines [12][13][14] . The most advanced candidate in this category is the protein vaccine P2-VP8*, which was developed at the NIH 15,16 and later advanced clinically by PATH [17][18][19] to an ongoing phase 3 efficacy trial (ClinicalTrials.gov identifier: NCT04010448).…”