Rotavirus vaccines performance: dynamic interdependence of host, pathogen and environment

Abstract

Introduction: As of January 2021, rotavirus vaccination programs have been implemented in 109 countries and their use has resulted in a positive impact on rotavirus-related diarrheal hospitalizations and mortality in children below five years of age. Despite these successes, several countries in Africa and Asia where disease burden is high have not yet implemented rotavirus vaccination at all or at a scale sufficient enough to demonstrate impact. This could be, among other reasons, due to poor vaccine coverage and the modest levels of efficacy and effectiveness of the vaccines in these resource-limited settings. Areas covered:We review various factors related to the human host (malnutrition, maternally-derived antibodies and breastfeeding, genetic factors, blood group and coadministration with oral polio vaccine), rotavirus pathogen (force of infection, strain diversity and coinfections) and the environment (related to the human microbiome) which reflect complex and interconnected processes leading to diminished vaccine performance in resource-limited settings. Expert opinion:Addressing the limiting factors for vaccine efficacy is needed but likely to take a long time to be resolved. An immediate solution is to increase the immunization coverage to higher values generating an overall effect of adequate proportion of protected population to reduce the prevalence of rotavirus disease.

Rotaviruses: From Pathogenesis to Disease Control—A Critical Review

“…The differences in vaccine effectiveness have also been observed in connection with oral polio and typhoid vaccines [ 191 ]. Several hosts, pathogen, and environmental factors have been suggested as the driving force for the discrepancies in vaccine performance between the two socioeconomic settings [ 7 , 192 ]. Other barriers to achieving the full potential of the vaccine for global rotavirus disease prevention include age restrictions on vaccine use, concern for safety attributed to intussusception and reversion to virulence in malnourished or immunosuppressed individuals due to the live attenuated nature of the vaccine virus, inhibitory effect of the maternally acquired antibodies against RV, and the cold chain storage requirement, which is difficult to maintain in low resource settings [ 67 ] ( Figure 3 ).…”

“…For instance, a mixed model study of the incidence of rotavirus infection in children from two low-resource settings in India and Malawi showed that children in the former were exposed to rotavirus at a much younger age than those in the latter [ 211 ]. In low resource settings, prevalent factors such as poor sanitation and hygiene, inadequate water supply, and low vaccine coverage have been shown to significantly contribute to higher RV transmission intensity and the early peak of RV incidence compared to their counterparts in high resource settings [ 7 ]. The early and multiple exposures to rotavirus orchestrated by the greater FOI can cause the production of an active immune response similar to maternal antibodies, which may impact vaccine response in infants [ 7 , 202 ].…”

“…In low resource settings, prevalent factors such as poor sanitation and hygiene, inadequate water supply, and low vaccine coverage have been shown to significantly contribute to higher RV transmission intensity and the early peak of RV incidence compared to their counterparts in high resource settings [ 7 ]. The early and multiple exposures to rotavirus orchestrated by the greater FOI can cause the production of an active immune response similar to maternal antibodies, which may impact vaccine response in infants [ 7 , 202 ]. Understanding and modifying the FoI between two socio-economic settings may provide the most direct, proximate, and actionable interventions such as providing an additional dose of vaccine [ 212 ], considering a neonatal dose schedule [ 213 ], or delaying a vaccine schedule [ 212 ] to improve or sustain vaccine response.…”

“…Several factors associated with the human host (e.g., malnutrition, histo-blood group antigens, ORV co-administration with polio vaccine and maternal factors), agents (e.g., genetic diversity, the force of infection and co-infection), and environment (enteropathy or dysbiosis of gut microbiome) have been suggested as possible etiologies driving the differences in vaccine-elicited protective immunity between the two socioeconomic settings [ 6 , 7 ]. With the emerging insights into structure–function relationships of RV proteins versus interactions with the host, this article provides information on past and present knowledge on the viral biology, pathogenic mechanisms, innate and adaptive immune response of the host, diagnosis, epidemiology and genetic diversity, and disease control through vaccination.…”

Transcriptomic Response to Perkinsus marinus in Two Crassostrea Oysters Reveals Evolutionary Dynamics of Host-Parasite Interactions

“…Host organisms need to evolve sophisticated defense mechanisms against parasites that constantly invent new ways to infect. Host-pathogen interactions are often dynamic, and the disease outcome is commonly dependent on multiple factors including the state of the host, the pathogenic potential of the pathogen and environmental conditions or stressors ( Allam et al, 2013 ; Debasish et al, 2021 ).…”