Intestinal mucosal immunity is unimportant for polio eradication: the failure of oral polio vaccination.

AIMS: To explore if intestinal immunity induced by infection with live viruses in the oral poliovirus vaccine (OPV) is essential, necessary or even helpful in interrupting transmission of wild poliovirus (WPV) for global polio eradication. METHODS: We reviewed the biology of virus-host interactions in WPV infection and its alterations by OPV-induced immunity for direct evidence of the usefulness of intestinal immunity. We also explored indirect evidence by way of the effect of the inactivated poliovirus vaccine (IPV) on the biology and on transmission dynamics of WPV. RESULTS: Immunity, systemic and intestinal, induced by infection with WPV or vaccine viruses, does not prevent re-infection with WPV or vaccine viruses respectively, when exposed. Such re-infected hosts shed virus in the throat and in faeces and are sources of further transmission. Immunity protects against polio paralysis-hence reinfection always remain asymptommatic and silent. CONCLUSION: Vaccine virus-induced intestinal immunity is not necessary for polio eradication. The continued and intensive vaccination efforts using OPV under the assumption of its superiority over IPV have resulted in the well-known undesirable effects, namely vaccine associated paralytic polio and the emergence of de-attenuated circulating vaccine-derived polioviruses, in addition to the delay in completing global WPV eradication.

Immunogenicity evaluation of primary polio vaccination schedule with inactivated poliovirus vaccines and bivalent oral poliovirus vaccine.

BACKGROUND: To assess the immunogenicity of the current primary polio vaccination schedule in China and compare it with alternative schedules using Sabin or Salk-strain IPV (sIPV, wIPV). METHODS: A cross-sectional investigation was conducted at four sites in Chongqing, China, healthy infants aged 60-89 days were conveniently recruited and divided into four groups according to their received primary polio vaccination schedules (2sIPV + bOPV, 2wIPV + bOPV, 3sIPV, and 3wIPV). The sero-protection and neutralizing antibody titers against poliovirus serotypes (type 1, 2, and 3) were compared after the last dose. RESULTS: There were 408 infants completed the protocol. The observed seropositivity was more than 96% against poliovirus types 1, 2, and 3 in all groups. IPV-only groups induced higher antibody titers(GMT) against poliovirus type 2 (Median:192, QR: 96-384, P<0.05) than the "2IPV + bOPV" group. While the "2IPV + bOPV" group induced significantly higher antibody titers against poliovirus type 1 (Median:2048, QR: 768-2048, P<0.05)and type 3 (Median:2048, QR: 512-2048, P<0.05) than the IPV-only group. CONCLUSIONS: Our findings have proved that the two doses of IPV with one dose of bOPV is currently the best polio routine immunization schedule in China.

Evolution of global polio eradication strategies: targets, vaccines, and supplemental immunization activities (SIAs).

BACKGROUND: Despite multiple revisions of targets and timelines in polio eradication plans since 1988, including changes in supplemental immunization activities (SIAs) that increase immunity above routine immunization (RI) coverage, poliovirus transmission continues as of 2024. METHODS: We reviewed polio eradication plans and Global Polio Eradication Initiative (GPEI) annual reports and budgets to characterize key phases of polio eradication, the evolution of poliovirus vaccines, and the role of SIAs. We used polio epidemiology to provide context for successes and failures and updated prior modeling to show the contribution of SIAs in achieving and maintaining low polio incidence compared to expected incidence for the counterfactual of RI only. RESULTS: We identified multiple phases of polio eradication that included shifts in targets and timelines and the introduction of different poliovirus vaccines, which influenced polio epidemiology. Notable shifts occurred in GPEI investments in SIAs since 2001, particularly since 2016. Modeling results suggest that SIAs play(ed) a key role in increasing (and maintaining) high population immunity to levels required to eradicate poliovirus transmission globally. CONCLUSIONS: Shifts in polio eradication strategy and poliovirus vaccine usage in SIAs provide important context for understanding polio epidemiology, delayed achievement of polio eradication milestones, and complexity of the polio endgame.

Enterovirus virus-like-particle and inactivated poliovirus vaccines do not elicit substantive cross-reactive antibody responses.

Human enteroviruses are the most common human pathogen with over 300 distinct genotypes. Previous work with poliovirus has suggested that it is possible to generate antibody responses in humans and animals that can recognize members of multiple enterovirus species. However, cross protective immunity across multiple enteroviruses is not observed epidemiologically in humans. Here we investigated whether immunization of mice or baboons with inactivated poliovirus or enterovirus virus-like-particles (VLPs) vaccines generates antibody responses that can recognize enterovirus D68 or A71. We found that mice only generated antibodies specific for the antigen they were immunized with, and repeated immunization failed to generate cross-reactive antibody responses as measured by both ELISA and neutralization assay. Immunization of baboons with IPV failed to generate neutralizing antibody responses against enterovirus D68 or A71. These results suggest that a multivalent approach to enterovirus vaccination is necessary to protect against enterovirus disease in vulnerable populations.

Trade-offs of different poliovirus vaccine options for outbreak response in the United States and other countries that only use inactivated poliovirus vaccine (IPV) in routine immunization.

Delays in achieving polio eradication have led to ongoing risks of poliovirus importations that may cause outbreaks in polio-free countries. Because of the low, but non-zero risk of paralysis with oral poliovirus vaccines (OPVs), countries that achieve and maintain high national routine immunization coverage have increasingly shifted to exclusive use of inactivated poliovirus vaccine (IPV) for all preventive immunizations. However, immunization coverage within countries varies, with under-vaccinated subpopulations potentially able to sustain transmission of imported polioviruses and experience local outbreaks. Due to its cost, ease-of-use, and ability to induce mucosal immunity, using OPV as an outbreak control measure offers a more cost-effective option in countries in which OPV remains in use. However, recent polio outbreaks in IPV-only countries raise questions about whether and when IPV use for outbreak response may fail to stop poliovirus transmission and what consequences may follow from using OPV for outbreak response in these countries. We systematically reviewed the literature to identify modeling studies that explored the use of IPV for outbreak response in IPV-only countries. In addition, applying a model of the 2022 type 2 poliovirus outbreak in New York, we characterized the implications of using different OPV formulations for outbreak response instead of IPV. We also explored the hypothetical scenario of the same outbreak except for type 1 poliovirus instead of type 2. We find that using IPV for outbreak response will likely only stop outbreaks for polioviruses of relatively low transmission potential in countries with very high overall immunization coverage, seasonal transmission dynamics, and only if IPV immunization interventions reach some unvaccinated individuals. Using OPV for outbreak response in IPV-only countries poses substantial risks and challenges that require careful consideration, but may represent an option to consider for some outbreaks in some populations depending on the properties of the available vaccines and coverage attainable.

Declaración SLIPE: Aumento de la cobertura antipoliomielítica con vacunas más seguras: una urgencia inaplazable en Latinoamérica / SLIPE Declaration: Increasing anti-polio coverage with safer vaccines: an urgent need that cannot be postponed in Latin America

Ante el riesgo real de ocurrencia de brotes de parálisis fláccida aguda en la región debidos a poliovirus derivado de la vacuna Sabin o a la importación de poliovirus salvaje, la Sociedad Latinoamericana de Infectología Pediátrica comisionó a un grupo ad hoc de expertos integrantes del Comité de Vacunas y Biológicos de la institución, para redactar un documento oficial de posición sobre la necesidad imperiosa de incrementar los niveles de inmunización contra la enfermedad en la región e incorporar definitivamente en forma exclusiva la vacuna de polio inactivada en todos los esquemas nacionales de vacunación. La presente publicación discute las principales conclusiones y recomendaciones generadas como resultado de esta actividad.

Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.

Increasing polio coverage with safer vaccines: a pressing need in Latin America

Given the actual risk of poliomyelitis outbreaks in the region due to poliovirus derived from the Sabin vaccine or the importation of wild poliovirus, the Latin American Society of Pediatric Infectious Diseases commissioned an ad hoc group of experts from the institution's Vaccines and Biologicals Committee, to draft an official position paper on the urgent need to increase immunization levels against the disease in the region and incorporate inactivated polio vaccine exclusive schedules in all national immunization programs. This publication discusses the main conclusions and recommendations generated as a result of such activity.

Ante el riesgo real de ocurrencia de brotes de parálisis fláccida aguda en la región debidos a poliovirus derivado de la vacuna Sabin o a la importación de poliovirus salvaje, la Sociedad Latinoamericana de Infectología Pediátrica comisionó a un grupo ad hoc de expertos integrantes del Comité de Vacunas y Biológicos de la institución, para redactar un documento oficial de posición sobre la necesidad imperiosa de incrementar los niveles de inmunización contra la enfermedad en la región e incorporar definitivamente en forma exclusiva la vacuna de polio inactivada en todos los esquemas nacionales de vacunación. La presente publicación discute las principales conclusiones y recomendaciones generadas como resultado de esta actividad.

Prevalence of neutralizing antibodies against poliovirus 1, 2, and 3 in healthcare professionals aged 20-50 years / Prevalência de anticorpos neutralizantes contra poliovírus 1, 2 e 3 em profissionais de saúde de 20 a 50 anos de idade

ABSTRACT Objective: To describe the prevalence of neutralizing antibodies against poliovirus (PV1, PV2, and PV3) in blood samples of healthcare professionals aged 20 to 50 years. Methods: Health professionals who serve children at Darcy Vargas Children's Hospital and the Department of Pediatrics of Irmandade da Santa Casa de São Paulo. The sample size was calculated at 323 participants. The Mantel-Haenszel chi-square was used to verify differences between groups. The neutralization reaction detected human poliovirus antibodies. For susceptible individuals, vaccination with the inactivated+triple acellular polio vaccine was performed, and neutralizing antibodies were re-dosed after one week. Results: 333 professionals were studied - 92.8% were immune to poliovirus 1, 86.5% to poliovirus 2, and 63.3% to poliovirus 3; 37% had titers less than 1:8 for any serotype, 5;1% had titers below 1:8 for all three. Vaccination with inactivated polio vaccine was performed for susceptible participants, and neutralizing antibodies were dosed after one week, showing increased titers for all polioviruses. Conclusions: Despite the detection of a significant percentage of individuals with low poliovirus antibody titer, the challenge with vaccination demonstrated immune response compatible with poliovirus immunity.

RESUMO Objetivo: Descrever a prevalência de anticorpos neutralizantes contra poliovírus (tipos 1, 2 e 3) em amostra de sangue de profissionais de saúde com idade de 20 a 50 anos. Métodos: Profissionais de saúde que atendem crianças do Hospital Infantil Darcy Vargas e do Departamento de Pediatria da Irmandade da Santa Casa de São Paulo. O tamanho da amostra foi de 323 participantes. Os anticorpos contra poliovírus humanos foram detectados pela reação de neutralização. Para os indivíduos suscetíveis, foram administradas vacina para poliomielite inativada+tríplice e nova dosagem de anticorpos neutralizantes após uma semana. Utilizou-se o teste do qui-quadrado de Mantel-Haenszel para verificar as diferenças entre os grupos. Resultados: Foram estudados 333 profissionais - 92,8% eram imunes ao poliovírus 1; 86,5%, ao poliovírus 2; 63,57%, ao poliovírus 3; 37% apresentaram títulos inferiores a 1:8 para qualquer sorotipo; 5,1% tinham títulos abaixo de 1:8 para os três. Após a vacinação dos suscetíveis, houve elevação dos títulos para todos os poliovírus. Conclusões: Apesar da detecção de percentual significativo de indivíduos com baixo título de anticorpos para poliovírus, o desafio da vacinação demonstrou resposta imune robusta compatível.

La vacuna polio oral en lactantes no interfiere con la detección de enterovirus en sangre / Oral polio vaccine in infants does not interfere in detection of enterovirus in blood

Introduction: There is not known if a viraemia post-oral polio vaccine (OPV) is detectable by modern molecular techniques. Such viraemia could affect the performance of the real time-polymerase chain reaction (PCR) for non polio enterovirus (EV) detection, technique of growing clinical use for the study of febrile infants. Objective: To determine viraemia post-first dose of OPV in healthy infants, by molecular techniques. Patients and Methods: 50 infants less than three months without previous VPO were randomized in 5 groups: a control group with pre-vaccination blood sample (BS), group 1 BS at day 2, group 2 BS at day 4, group 3, BS at day 6 and group 4, BS at day 8 post-vaccination. Conventional and specific PCR for poliovirus and real time PCR for non polio EV were performed in BS and in OPV samples. Results: No genetic material of poliovirus was detected in any infant, while in 9 of them (18%) non polio EV was identified. Real time PCR for EV did not amplify poliovirus from OPV samples. Discussion: Results suggest that no post VPO viraemia detectable by molecular methods exists. Considering that real time PCR for EV does not allow to identify polio virus, no false positives of the test are expected as a result of a recent VPO vaccination. We documented presence of non polio EV in blood of healthy asymptomatic infants.

Introducción: No existen estudios que indiquen si la vacuna polio oral (VPO) produce viremia detectable mediante métodos moleculares. Una eventual viremia podría afectar el rendimiento de la RPC tiempo real para detectar enterovirus (EV) no polio, examen de creciente uso clínico en lactantes pequeños con fiebre sin foco. Objetivo: Determinar viremia post VPO en lactantes sanos, por métodos moleculares. Métodos: 50 menores de 3 meses, al momento de recibir su primera VPO se distribuyeron en forma aleatoria en 5 grupos: control, muestra de sangre pre-vacunación; grupo 1, muestra al 2° día; grupo 2, al 4° día; grupo 3, al 6° día y grupo 4, al 8° día post-vacunación. Se realizó RPC convencional específica para virus polio y RPC tiempo real para EV no polio en las muestras de sangre y en muestras de VPO. Resultados: No se identificó presencia de material genético de virus polio en lactante alguno, mientras que en 9 (18%) se identificó presencia de EV no polio. La RPC tiempo real para EV no polio no amplificó material genético a partir de las muestras de VPO. Discusión: Los resultados sugieren que no existe viremia post-VPO detectable por métodos moleculares. Considerando que la RPC tiempo real de EV no polio de uso clínico no permite identificar la presencia de virus polio, estos hallazgos indican que no existirán falsos positivos de este examen como resultado de una vacunación VPO reciente. Adicionalmente se documentó presencia de EV no polio en sangre de lactantes asintomáticos.

A RT-PCR method for selective amplification and phenotypic characterization of all three serotypes of Sabin-related polioviruses from viral mixtures

Outbreaks caused by vaccine-derived polioviruses are challenging the final eradication of paralytic poliomyelitis. Therefore, the surveillance of the acute flaccid paralysis cases based on poliovirus isolation and characterization remains an essential activity. Due to the use of trivalent oral poliovirus vaccine (OPV), mixtures containing more than one serotype of Sabin-related polioviruses are frequently isolated from clinical samples. Because each poliovirus isolate needs to be individually analyzed, we designed polymerase chain reaction primers that can selectively distinguish and amplify a genomic segment of the three Sabin-related poliovirus serotypes present in mixtures, thus, optimizing the diagnosis and providing prompt information to support epidemiologic actions.

Ausencia de circulación de poliovirus en departamentos colombianos con coberturas vacunales inferiores a 80% / Absence of poliovirus circulation in Colombian departaments with vaccination coverage below 80%

El presente estudio se propuso explorar la posible circulación silente de poliovirus salvajes y derivados de la vacuna (VDPV, por sus siglas en inglés), en departamentos de Colombia con cobertura de vacunación para polio (OPV, por sus siglas en inglés) menor de 80%. Se colectaron 52 muestras de aguas residuales que se concentraron mediante precipitación con polietilenglicol y cloruro de sodio. La detección viral se realizó mediante aislamiento y la identificación por neutralización del efecto citopático, así como mediante reacción en cadena de la polimerasa convencional y en tiempo real, posterior a la transcripción reversa (TR-RCP y rTR-RCP). Los poliovirus aislados se caracterizaron por secuenciación del gen VP1. En dos de las 52 muestras hubo presencia de poliovirus Sabin 2 con más de 99% de similitud de secuencia con la cepa OPV Sabin 2. Se detectó circulación de enterovirus no polio en 17,3% de las muestras. Los serotipos identificados correspondieron a coxsackievirus B1, echovirus 30 y echovirus 11. No se detectaron evidencias de circulación de VDPV ni poliovirus salvaje en los departamentos de Colombia con coberturas de OPV inferiores a 80%.

This study aims to explore a possible silent circulation of wild and vaccine-derived polioviruses in departments of Colombia with polio vaccination coverage of below 80%. The study collected 52 samples of wastewater concentrated as a result of precipitation with polyethylene glycol and sodium chloride. The viral detection was carried out through isolation and the identification through neutralization of the cytopathic effect, as well as through a conventional polymerase chain reaction following reverse transcription. The isolated polioviruses were characterized by the VP1 gene sequence. In two of the 52 samples, there was a presence of the Sabin type 2 poliovirus with more than 99% sequence similarity with the Sabin type 2 strain polio. Circulation of the nonpolio enterovirus was detected in 17.3% of the samples. The serotypes identified corresponded to coxsackievirus B1, echovirus 30, and echovirus 11. No evidence of the spread of either vaccine-derived poliovirus or wild poliovirus was detected in the departments of Colombia with polio coverage lower than 80%

Recombinant viruses as vaccines against viral diseases

Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

Nucleotide sequences of the VP1 capsid proteins of wild poliovirus types 1 and 3 from epidemic areas of Brazil

The nucleotide sequences encoding the capsid protein VP1 were determined for the wild polioviruses of serotypes 1 and 3 endemic to the northeastern region of Brazil. Compared with the corresponding Sabin vaccine strain sequences, the wild isolates differed at 20%(type 1) and 22%(type 3) of their nucleotide positions, and in 7%(type 1) and 11%(type 3) of their amino acid residues. The highest degree of amino acid heterogeneity occurred within the amino-terminal residues of the VP1 proteins. Intratypic amino acid differences also occurred in VP1 surface residues that form parts of antigenic sites for neutralizing antibodies