Heterologous vaccination interventions to reduce pandemic morbidity and mortality: Modeling the US winter 2020 COVID-19 wave

COVID-19 remains a stark health threat worldwide, in part because of minimal levels of targeted vaccination outside high-income countries and highly transmissible variants causing infection in vaccinated individuals. Decades of theoretical and experimental data suggest that nonspecific effects of non–COVID-19 vaccines may help bolster population immunological resilience to new pathogens. These routine vaccinations can stimulate heterologous cross-protective effects, which modulate nontargeted infections. For example, immunization with Bacillus Calmette–Guérin, inactivated influenza vaccine, oral polio vaccine, and other vaccines have been associated with some protection from SARS-CoV-2 infection and amelioration of COVID-19 disease. If heterologous vaccine interventions (HVIs) are to be seriously considered by policy makers as bridging or boosting interventions in pandemic settings to augment nonpharmaceutical interventions and specific vaccination efforts, evidence is needed to determine their optimal implementation. Using the COVID-19 International Modeling Consortium mathematical model, we show that logistically realistic HVIs with low (5 to 15%) effectiveness could have reduced COVID-19 cases, hospitalization, and mortality in the United States fall/winter 2020 wave. Similar to other mass drug administration campaigns (e.g., for malaria), HVI impact is highly dependent on both age targeting and intervention timing in relation to incidence, with maximal benefit accruing from implementation across the widest age cohort when the pandemic reproduction number is >1.0. Optimal HVI logistics therefore differ from optimal rollout parameters for specific COVID-19 immunizations. These results may be generalizable beyond COVID-19 and the US to indicate how even minimally effective heterologous immunization campaigns could reduce the burden of future viral pandemics.

Retrospective Analysis of Six Years of Acute Flaccid Paralysis Surveillance and Polio Vaccine Coverage Reported by Italy, Serbia, Bosnia and Herzegovina, Montenegro, Bulgaria, Kosovo, Albania, North Macedonia, Malta, and Greece

Here we analyzed six years of acute flaccid paralysis (AFP) surveillance, from 2015 to 2020, of 10 countries linked to the WHO Regional Reference Laboratory, at the Istituto Superiore di Sanità, Italy. The analysis also comprises the polio vaccine coverage available (2015–2019) and enterovirus (EV) identification and typing data. Centralized Information System for Infectious Diseases and Laboratory Data Management System databases were used to obtain data on AFP indicators and laboratory performance and countries’ vaccine coverage from 2015 to 2019. EV isolation, identification, and typing were performed by each country according to WHO protocols. Overall, a general AFP underreporting was observed. Non-Polio Enterovirus (NPEV) typing showed a high heterogeneity: over the years, several genotypes of coxsackievirus and echovirus have been identified. The polio vaccine coverage, for the data available, differs among countries. This evaluation allows for the collection, for the first time, of data from the countries of the Balkan area regarding AFP surveillance and polio vaccine coverage. The need, for some countries, to enhance the surveillance systems and to promote the polio vaccine uptake, in order to maintain the polio-free status, is evident.

Assessment of Strengths and Weaknesses of Inactivated Polio Vaccine Practices in Qasimabad, Pakistan

Objectives: The objectives of the study were to assess the strengths and weaknesses of inactivated polio vaccine (IPV) practices in Qasimabad, Pakistan. Material and Methods: This cross-sectional survey study was conducted in Hyderabad, Sindh, from June 22, 2017, to September 22, 2017. It included seven expanded programs on immunization (EPI) centers in Taluka Qasimabad, as well as outreach settings. Data were collected through convenience sampling with the help of an EPI Monitoring Checklist and a pre-designed questionnaire. Statistical Package for the Social Sciences version 23.0 was used for the descriptive analysis. Results: Six of the seven health facilities were found to be screening for missed opportunities. During power outages or load shedding, the majority of EPI centers (85.7%) had a backup plan in place. However, the major shortcoming was the failure to obtain parental consent before vaccination by vaccinators at all 7 (100%) EPI centers. At 5 (71.9%) of the centers, outreach activities to vaccinate children were organized, and IPV was only given to infants at 1 (19.2%) of the sessions. The vaccinator opened the vial before using it, and the used IPV vial was not discarded at the end of the outreach session. Because one center’s vaccinator was female (19.2%), and another center’s vaccinator was single (19.2%), no outreach activity was planned at those two locations. Conclusion: This research highlights the benefits and drawbacks of the current EPI program for the IPV vaccine. The presence of EPI centers at all health facilities, as well as the availability of IPV and cold chain equipment, as well as permanent and fully-trained employees, are some of the most important strengths. Lack of pre-service training and adverse events following immunization vaccine training were identified as weaknesses. There are a lack of IPV refresher training, as well as improper arrangements for outreach vaccination sessions, and a lack of transportation for vaccinators.

Tingkat Pengetahuan Mahasiswa Fakultas Kedokteran Universitas Yarsi Mengenai Penggunaan Human Diploid Cell Dalam Proses Produksi Vaksin Polio

Latar Belakang : Vaksin merupakan suspensi mikroorganisme yang dilemahkan atau dimatikan, atau protein antikgenik dari berbagai organisme tadi yang diberikan untuk mencegah, meringankan, atau mengobati penyakit-penyakit menular. Vaksin pertama kali tercatat pada tahun 1769, yang dipublikasikan oleh Edward Jenner, yaitu specimen yang berasal dari lesi lengan seseorang yang terinfeksi Cowpox. Human Diploid Cells (HDC) merupakan salah satu sel yang digunakan untuk mengkultur virus yang akan dijadikan vaksin. HDC yang berasal dari aborsi manusia ini banyak digunakan untuk mengkultur virus Polio IPV dan OPV, Rabies, Rubella, Measles, Varicella-Zooster, dan Hepatitis A. Tujuan : Vaksin polio merupakan vaksin yang diwajibkan pada anak yang dijadwalkan dari Ikatan Dokter Anak Indonesia (IDAI) yang dibagi menjadi dua jenis, IPV (Inactivated Polio Vaccine) dan OPV (Oral Polio Vaccine). Metode : Jenis Penelitian yang digunakan adalah deskriptif dengan pendekatan cross sectional menggunakan kuesioner. Populasi yang digunakan adalah mahasisa Fakultas Kedokteran Universitas YARSI tahun pertama dan tahun ketiga yang memenuhi syarat. Cara pemilihan sampel dengan simple random sampling. Hasil : Penelitian yang dilaksanakan selama 3 hari dengan menggunakan kuesioner, dari 100 responden didapatkan persentase jumlah kuesioner Pengetahuan mengenai Human Diploid Cell berdasarkan Tingkat Pendidikan didapatkan pengetahuan baik sebanyak 5% pada tahun ketiga dan 7% pada tahun pertama. Pengetahuan cukup sebanyak 23% pada tingkat ketiga dan 28% pada tahun pertama. Pengetahuan kurang sebanyak 9% pada tingkat ketiga dan 28% pada tahun pertama. Persentase jumlah kuesioner Pengetahuan mengenai Polio berdasarkan Tingkat Pendidikan didapatkan pengetahuan baik sebanyak 15% pada tahun ketiga dan 19% pada tahun pertama. Pengetahuan cukup sebanyak 18% pada tingkat ketiga dan 31% pada tahun pertama. Pengetahuan kurang sebanyak 4% pada tingkat ketiga dan 13% pada tahun pertama. Kesimpulan : Tidak terdapat hubungan antara tingkat pendidikan dengan pengetahuan mengenai Human Diploid Cell dalam vaksin Polio. Dalam pandangan Islam, penggunaan vaksin Polio hukumnya mubah karena prinsip Dharuriyat bertujuan untuk mempertahankan nyawa atau Hifdz an-nafs anak dari ancaman penyakit.

A review on medicinal plants as potential sources of natural immunomodulatory action

The concept of immunomodulation was proposed by Edward Jenner, while working on polio vaccine in 1796. A brawny, fine-functioning immune system is the keystone of excellent health. Immune replies are the consequence of an effectual interaction among innate (natural and non-specific) and acquired (adaptive and specific) components of the immune system. Inequity or failure of the immune systems is connected with a variety of chronic illness counting allergies, autoimmune diseases, cancers and furthers. Diverse innate and adaptive immune cells that are incorporated in this multifaceted networking organization may symbolize talented targets for expanding immunotherapeutics for treating specific immune illness. An assorted array of natural, synthetic, and recombinant compounds is accessible with both advantages and demerits. A range of phytochemicals have been remote, differentiated and customized for expansion and employ as avoidance or cure of human diseases, but the request of customary or novel medicinal plants for employ as immunomodulators in indulgencing immune diseases is still comparatively limited. At present, there is much-growing interest in the use of medicinal plants as modulators of the complex immune system. Numerous therapeutic consequences of plant extracts have been recommended to be because of their extensive assortment of immunomodulatory effects and persuade on the immune system of the human body. In present review paper, various medicinal plants, their resultant crude or fractionated phyto extracts and the precise phytochemicals remote from them are conversed in terms of their immunomodulatory bioactivities. We also review their possible for future expansion as immunomodulatory or inflammation-regulatory therapeutics or agents. Keywords: Immunomodulation, Immune system, Phytochemicals, Medicinal plant, Plant extracts

The Evolution of Competition

Human competition is, at least partially, responsible for some of the transcended achievements of the species (walking on the moon, the polio vaccine, etc.), but the forces unleashed by competition have also led to profound human suffering (warfare, domination of one group by another group, etc.). In this article, the authors approach competition from an evolutionary perspective, applying Darwin’s theories of natural and sexual selection to understand better the nature of human competition. From the perspective of evolutionary psychology, humans engage in competition to gain resources, including status, food, and mating opportunities. Males tend to engage in more overt and aggressive forms of competition than females, but both sexes desire access to material and cultural goods associated with reproductive fitness. In the last roughly seventy years, the nature of men’s competition has transformed dramatically leading to declines in both within and between-group violence. As developed societies have succeeded in suppressing more overt and destructive forms of male–male competition, men attempt to gain status through occupational success, cognitive sophistication, moral signaling, and other relatively nonviolent behaviors. In this sense, men’s and women’s competition is more similar than it was a century ago. However, women’s competition is still less visible and relies on more indirect mechanisms (e.g., spreading gossip, subtle use of body language). For this reason, female–female competition has attracted less study than male–male competition. Fortunately, in the last decade, psychologists have partially redressed this imbalance.

Age-appropriate vaccination coverage and its determinants in children aged 12–36 months in Nepal: a national and subnational assessment

Background Vaccination is one of the effective ways to develop immunity against potential life-threatening diseases in children in early age. This study is focused on analysing the age-appropriate vaccination coverage at national and subnational levels and identify the factors associated with age-appropriate coverage in Nepal. Methods 460 children aged 12–36 months were included in the study. The data was obtained from Nepal Demographic and Health Survey (NDHS) 2016–17. Age-appropriate coverage of Bacillus Calmette-Guerin vaccine (BCG), oral polio vaccine (OPV) doses 1–3, pentavalent vaccine (PE) doses 1–3, and first dose of measles, mumps, and rubella vaccine (MMR) were estimated using Kaplan Meier method. Multilevel logistic regression with random intercept was used to identify the factors associated with age-appropriate vaccination. Results The crude coverage of the vaccines included in the study ranged from 91.5% (95% CI, 88.5–93.7) for PE3 to 97.8% (95.8–98.7) for BCG. Although the crude coverage of all the vaccines was above 90%, the age-appropriate coverage was significantly low, ranging from 41.5% (36.5–46.6) for PE3 to 73.9% (69.2–78.1) for PE1. Furthermore, high disparity in timely vaccination coverage was observed at regional level. Compared to the age-appropriate vaccination coverage in other provinces, Province 2 had the lowest coverage of all, followed by that in Province 6. The timeliness of vaccination was significantly associated with subnational regions i.e., provinces and the season of childbirth. Conclusion Although the immunization program in Nepal has achieved the target of 90% crude coverage of all the childhood vaccines, the age-appropriate coverage is significantly low which undermines the effectiveness of the vaccines administered. Thus, along with crude coverage, timeliness of the vaccines administered should be taken into consideration and thoroughly monitored at national and subnational levels. Provincial government should formulate tailored strategies to ensure the timely administration of the childhood vaccines.

739 Intratumor childhood vaccine-specific CD4+ T cell recall helps antitumor CD8 T cells

BackgroundPVSRIPO, a recombinant poliovirus derived from the live-attenuated Sabin oral polio vaccine strain, is being tested in multi-institutional phase II clinical trials for recurrent glioblastoma (NCT04479241) and unresectable, PD-1 refractory melanoma (NCT04577807) in combination with PD1 blockade. PVSRIPO capsid is identical to the Sabin vaccine strain and >99% identical to the inactivated Polio vaccine (IPOL, Salk), against which public health mandated childhood vaccination is near universal. In non-vaccinated mice, PVSRIPO mediates antitumor efficacy in a replication-dependent manner via engaging innate inflammation and antitumor T cells. Accordingly, it is anticipated that pre-existing immunity to PVSRIPO impedes antitumor therapy. However, recent evidence indicates that immunological 'recall', or reactivation of memory T cells, may mediate anti-tumor effects.MethodsThe impact of prior polio vs control (KLH) vaccination on intratumor viral replication, tumor inflammation, and overall tumor growth after intratumor PVSRIPO therapy was assessed in murine tumor models. The role of polio capsid and tetanus recall antigens in mediating intratumor inflammation and antitumor efficacy was similarly studied in mice non-permissive to PVSRIPO infection. To mechanistically define antitumor effects of polio recall, B cell and CD8 T cell knockout mice were used, in addition to adoptive transfer of CD4+ T cells from vaccinated mice. Intratumor polio or tetanus recall antigen therapy was performed after OT-I transfer (OVA-specific T cells) in the B16-OVA melanoma model to gauge antitumor T cell activity. Lastly, the inflammatory effects of polio and tetanus antigens was tested in human peripheral blood mononuclear cells (PBMCs).ResultsDespite curtailing intratumor viral replication, prior polio vaccination in mice potentiated subsequent antitumor efficacy of PVSRIPO. Intratumor recall responses induced by polio and tetanus antigens also delayed tumor growth. Recall antigen therapy was associated with marked intratumor influx of eosinophils, conventional CD4+ T cells, and increased expression of IFN-g, TNF, and Granzyme B in tumor infiltrating T cells. The antitumor efficacy of polio recall antigen was mediated by CD4+ T cells, partially depended upon CD8+ T cells, and was impaired by B cells. Both polio and tetanus recall antigen therapy bolstered the antitumor function of tumor-specific OT-I CD8+ T cells. Polio and tetanus antigens induced CXCL10 and type I/II/III IFNs in PBMCs in vitro.ConclusionsChildhood vaccine-specific CD4+ T cells hold cancer immunotherapy potential. In the context of PVSRIPO therapy, antitumor and inflammatory effects of polio vaccine-specific CD4+ T cell recall supersedes inhibitory effects of attenuated intratumor viral replication, and represents a novel mechanism of action.Ethics ApprovalThe animal work described in this study was approved by the Duke University IACUC.

Knowledge, attitude, and barriers toward polio immunization among pre-clinical students in Malaysia

Background: Polio is reported as reemerging disease in Malaysia after 27 years of being free from it. It is important to identify the awareness towards polio vaccine among the medical students who are the future and the pillars of the nation, to develop a country. Aims and Objectives: This study aims to assess the knowledge, attitude, and barriers toward polio immunization among pre-clinical medical students. Materials and Methods: A cross-sectional study was conducted among 190 pre-clinical students from a private university after obtaining informed consent and institutional ethical clearance. Data collected from Google Forms questionnaire were analyzed using SPSS version 20. Results: Insufficient knowledge, especially on disease nature, transmission, and correct dosage of vaccine, was noticed. Findings revealed that 79.5% of the students showed unfavorable attitude toward polio immunization. Year 2 students are more positive toward the vaccination compared to year 1. Main barriers toward polio immunization selected by the respondents are disagreement from the spouse, insecure about vaccine safety, and distance of the health center. Conclusion: Pre-clinical students should enhance their knowledge to be able to recognize the various barriers of polio immunization in our country and be part of the effort in solving these barriers as polio eradication is critical to ensuring a healthier future for children.