Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3

Abstract

Vaccination with Sabin, a live attenuated oral polio vaccine (OPV), results in robust intestinal and humoral immunity and has been key to controlling poliomyelitis. As with any RNA virus, OPV evolves rapidly to lose attenuating determinants critical to the reacquisition of virulence1–3 resulting in vaccine-derived, virulent poliovirus variants. Circulation of these variants within underimmunized populations leads to further evolution of circulating, vaccine-derived poliovirus with higher transmission capacity, representing a significant risk of polio re-emergence. A new type 2 OPV (nOPV2), with promising clinical data on genetic stability and immunogenicity, recently received authorization from the World Health Organization for use in response to circulating, vaccine-derived poliovirus outbreaks. Here we report the development of two additional live attenuated vaccine candidates against type 1 and 3 polioviruses. The candidates were generated by replacing the capsid coding region of nOPV2 with that from Sabin 1 or 3. These chimeric viruses show growth phenotypes similar to nOPV2 and immunogenicity comparable to their parental Sabin strains, but are more attenuated. Our experiments in mice and deep sequencing analysis confirmed that the candidates remain attenuated and preserve all the documented nOPV2 characteristics concerning genetic stability following accelerated virus evolution. Importantly, these vaccine candidates are highly immunogenic in mice as monovalent and multivalent formulations and may contribute to poliovirus eradication.

Viruses associated with measles-like illnesses in Uganda

“… 34 Sabin-like poliovirus, as detected in this study (poliovirus derived from vaccine) is not associated with reversion mutations or neurotropic disease. 35 In this case, we detected a poliovirus that was identical within the Sabin 1 VP1 gene and was therefore a Sabin-like poliovirus type 1. It occurred in a 16-year old who had not recently received poliovirus vaccination and therefore is likely to have acquired the infection from a recently vaccinated contact.…”

Two centuries of vaccination: historical and conceptual approach and future perspectives

“…On rare occasions, vaccination with the live attenuated virus could result in paralytic poliomyelitis—a condition termed vaccine-associated paralytic poliomyelitis (VAPP) or mutate to a more virulent strain causing small outbreaks of vaccine-derived poliovirus (VDPV). Despite these potential risks, the benefits of OPV resulted in its widespread adoption in Western regions, and it was instrumental in extensive vaccination campaigns that significantly decreased the global incidence of polio ( 12 , 13 ).…”

“…In 2016, a global coordinated shift occurred from trivalent OPV (tOPV), containing Sabin strain types 1, 2, and 3, to bivalent OPV (bOPV), containing Sabin strain types 1 and 3. Remarkably, clinical cases of wild poliovirus have decreased by over 99% since 1988, with an estimated 350,000 cases in more than 125 endemic countries compared to only 6 cases reported in 2021 ( 12 , 13 , 138 ). Today, wild poliovirus type 1 is endemic only in Afghanistan and Pakistan, but there has been a rise in circulating vaccine-derived poliovirus type 2 outbreaks since 2017.…”

Immunogenicity and safety of a live-attenuated SARS-CoV-2 vaccine candidate based on multiple attenuation mechanisms

“…In fact, vaccine-derived paralytic polio was reported 38 years after the vaccine had been introduced, representing a threat to uninfected populations (Macklin et al, 2020). Advances in our basic knowledge of viruses have enabled the design of attenuated strains, such as that in the new type 2 oral polio vaccine (nOPV2), which is associated with a reduced risk of reversion due to genome modification (Yeh et al, 2020; Yeh et al, 2023). nOPV2 was recently approved by the World Health Organization, indicating that live-attenuated vaccines that overcome the risk of reversion are still in demand.…”