Valuation of Two Serological Tests in the Estimation of Rabies Virus Antibodies among Free-Ranging Vaccinated Dogs in Bengaluru, India | Chapter 2 | Innovations in Biological Science Vol. 4

 

Rabies is a zoonotic viral disease caused by an RNA virus in the genus Lyssavirus of the family Rhabdoviridae. The disease is endemic in most African and Asian countries. Globally, rabies kills tens of thousands of people annually, and domestic dogs transmit most (99%) cases. Vaccination is the practical solution for the prevention of rabies in dogs. Assessment of the immunogenicity of vaccination includes estimation of specific rabies virus neutralizing antibodies (VNA) in the target species.

 

We undertook a study to estimate the levels of VNA in free-roaming dogs with a history of rabies vaccination in Bengaluru city, India. We compared the rapid fluorescent focus inhibition test (RFFIT) and an in-house quantitative indirect ELISA (iELISA). The effectiveness of iELISA was evaluated using a two-tailed Spearman correlation analysis by comparing it with RFFIT. The study area comprised the jurisdiction of Bruhat Bengaluru Mahanagara Palike (BBMP), the Bengaluru civic body. The BBMP, along with several non-government organizations (NGOs), was conducting a trap-neuter-vaccinate-release program for the prevention of dog rabies. Serum samples were collected from 250 free-roaming dogs from representative regions of BBMP, of which 125 had a VNA titre of 0.5 IU or more by the RFFIT. Furthermore, 126 dogs showed percent positivity values (PP values) more than the cut-off PP value of 57.1 by the iELISA, accounting for 50.4% of satisfactory post-vaccinal serum conversion. The sensitivity and specificity of the ELISA was 94.4% and 95.2%, respectively. Based on these data, a quantitative ELISA may be a complementary tool for sero-monitoring immune responses of free-ranging animals after rabies vaccination. The study also recommends the need for enhanced rabies surveillance for the detection of rabies occurrence as a part of the National Action Plan for Rabies Elimination (NAPRE).

 

 

Author(s) Details

 

Lekshmi J. Das
KVAFSU-CVA Rabies Diagnostic Laboratory, Department of Microbiology, Veterinary College, KVAFSU, Bengaluru 560024, India.

 

 

Please see the book here:-https://doi.org/10.9734/bpi/ibs/v4/7568B

COVID-19 Vaccine Acceptance among Health Care Providers in Rural Areas of Northern State, Sudan | Chapter 1 | Pharmaceutical Research: Recent Advances and Trends Vol. 6

 

Aim: The present study assessed the adherence to the COVID-19 vaccine among healthcare providers in Rural Areas in the Northern State of Sudan.

 

Background: Control of coronavirus disease (COVID-19) through vaccination is not merely dependent on vaccine efficacy and safety. Instead, the vaccine also needs to have health professionals and general public acceptance for successful control of the virus.

 

Methodology: A descriptive cross-sectional study was conducted at Merowe Hospital in a rural area in the Northern state of Sudan; the hospital offers medical and health services for many villages around the hospital, and the study period was extended from December 2021 to March 2022. The study was carried out among 108 participants; they were selected using a purposive sampling technique. Data were collected via a questionnaire. Data was entered into SPSS version 25. Analysis was done using frequency tables and cross-tabulations; significance was considered at P ≤ 0.05.

 

Results: The study found that 52.8% were not vaccinated, while 72.2% of total participants would recommend the COVID-19 vaccine to their family, friends, and patients, and 53.7% said that they had contributed to community campaigns to encourage people to get the vaccine,64.7% of vaccinated participants took the vaccine because they were afraid of occupational hazards, 27.8% their respond about vaccine effect in prevention was negative and there was a significant association between profession and contribution in community campaign P-value equal to 0.035. The finding indicates that the major obstacle to vaccination adherence and acceptance is a lack of reliable information, a challenge that authorities could address quickly. By providing comprehensive and accurate vaccine information, authorities could significantly improve vaccination adherence, acceptance, and coverage.

 

Conclusion: Nearly half of the participants (47.2%) were immunized. Getting enough and correct information about the vaccines that the available was the main aspect that could enhance vaccination uptake. The current analysis offers the authorities profound insights into the anticipated challenges, issues, and potential courses of action. Efficient and evidence-based measures to encourage the use of the COVID-19 vaccine among healthcare providers are urgently required.

 

Author (s) Details

Nadia Ahmed Mohammed Hamad

Faculty of Medicine and Health Sciences, Merowe University of Technology, Sudan.

 

Amal Mohammed Hamid
Prince Sultan Military College of Health Sciences, Dammam, Saudi Arabia.

 

Amal Abdelgadir Mohame
College of Applied Medical Science, Taif University, Saudi Arabia.

 

Khalida Hussain Saeed Sharaf
Vision Medical College in Jeddah, Saudi Arabia.

 

Please see the book here:- https://doi.org/10.9734/bpi/prrat/v6/1883

 

Concise Teleost Immunology | Book Publisher International

 

This book is based on an overview of fish biology followed by inducer nature, genetic and immune molecules, receptors, cells, tissues and organs of the teleost fish immune system in comparison to that of mammals. In addition to special chapters on the nature of normal, subnormal and abnormal immune responses. Together with immunity to infection and vaccination. The text contains 5  parts, 10 sections and 26 chapters.

 

 

Author (s) Details

Professor Emeritus Dr. Ibrahim Shnawa
Deparment of Medical Biotechnology, College of Medical Biotechnology, AL-Qasim Green University, Babylon, Iraq and College of Nursing Technichians, Hilla University College, Babylon, Iraq.

 

Please see the book here:- https://doi.org/10.9734/bpi/mono/978-93-48006-31-8

 

Varying Behavioral Attitudes and Correlates of HPV Infection among Young Adolescents in Benue State, Nigeria: A Cross-Sectional Study | Chapter 1 | Achievements and Challenges of Medicine and Medical Science Vol. 3

Aim: This study aims to assess the knowledge of HPV infection and the practice of primary prevention, the willingness of HPV uptake, and attitudinal differences and correlates among randomly sampled secondary school students across the three senatorial districts of Benue State, Nigeria.

Background: Human Papillomavirus (HPV) infection is a significant public health concern globally, especially in low- and middle-income countries. It is one of the most prevalent sexually transmitted infections (STIs). In Africa, including Nigeria, HPV prevalence is high, contributing to a substantial burden of cervical cancer. Despite challenges, massive HPV vaccination campaigns in Africa show promise for preventing cervical cancer cases. In Benue State, Nigeria, limited research exists on several aspects of HPV knowledge and attitudes towards HPV among secondary school students.                                                                                                                                                   Methods: The cross-sectional study was conducted among adolescents aged 10–19 years in six secondary schools in three local government areas (LGAs) in Benue State, Nigeria. Two-stage sampling was used to select the LGAs and schools, with a final sample size of 591 students. Within these schools, students were recruited using simple random sampling, which gives every student an equal chance of being selected, ensuring fair representation. The selected schools represent both junior and senior secondary school levels and span across the three senatorial districts of the state. Data were collected using a self-administered questionnaire covering sociodemographic characteristics, HPV knowledge, prevention practices, and willingness for HPV vaccination. Statistical analyses included univariate analyses and tests of association, with significance set at p < 0.05 or 0.001 depending on the level of the stringency of the evidence required. Data were analysed using SPSS version 25.       

Results: This study found a statistically significant median difference in the perceived knowledge that HPV infection is a sexually transmitted infection (STI) based on age. Only 35.4% of the participants were males, and 86.8% were between the ages of 10 and 16. Only 24.7% acknowledged that HPV can be transmitted during sexual intercourse, and 36.2% recognized that HPV can be transmitted via skin-to-skin contact. In the survey, 48.1% noted that HPV can cause cervical cancer. Around half (50.9%) acknowledged that early sexual debut increases the risk of acquiring HPV, while only 28.1% recognized vaccination as a preventive strategy against HPV infection. Only 35% correctly stated the best time for the HPV vaccine. In assessing the practice of HPV prevention, 14.9% are in a sexual relationship and 10.3% admitted to not using condoms during sexual intercourse. Also, 11.8% have had STIs, and 27.2% have previously undergone HIV screening. Various bivariate analyses showed some varying behavioural differences and correlates of HPV infection among young adolescents in Benue State, Nigeria.

  Conclusions: This study provides valuable insights into HPV knowledge, prevention practices, and willingness to uptake HPV vaccination among secondary school students in Benue State, Nigeria. The significance of the differences and correlates was discussed using themes. The research has unpacked complex relationships that could have public health implications for researchers and policymakers. Moreover, ten actionable policy recommendations were prescribed. Several interventions and areas for further study were proposed. The study also recommended that public health campaigns can leverage existing infrastructure, and healthcare providers can play a key role in raising HPV awareness.

 

Author (s) Details

Evelyn Erdoo Orya
Sydani Group, Abuja, Nigeria.

 

Kayode Khalid Bello
Federal Medical Centre, Keffi, Nasarawa State, Nigeria.

 

Sidney Sampson
Sydani Group, Abuja, Nigeria.

 

Esther Awazzi Envuladu
Jos University Teaching Hospital, Katon Rikkos, Plateau State, Nigeria.

 

Hilary I. Okagbue
Sydani Institute for Research and Innovation, Sydani Group, Abuja, Nigeria.

 

Please see the book here:- https://doi.org/10.9734/bpi/acmms/v3/2627

Mpox (Monkeypox): A Comprehensive Overview | Chapter 5 | Disease and Health: Research Developments Vol. 6

Monkeypox is a zoonotic viral disease caused by the Monkeypox virus (MPXV), a member of the Orthopoxvirus genus. Initially identified in 1958 in research monkeys, the first human case was identified in 1970 in the Democratic Republic of Congo (DRC). Monkeypox primarily impacts Central and West African regions but has emerged globally as a public health concern, with outbreaks occurring in non-endemic nations. The disease manifests with influenzae-like symptoms, fever, lymphadenopathy, and a distinctive rash that evolves from macules to papules, vesicles, and pustules. Transmission occurs through close contact with infected individuals, body fluids, respiratory droplets, or contaminated surfaces. Zoonotic transmission originates from interaction with diseased animals, especially rats, considered to be the principal reservoirs. The 2022 multi-country outbreak highlighted the risk of human-to-human transmission in highly populated areas and among susceptible groups, including immunocompromised adults and children. The management of monkeypox is supportive, emphasising symptom alleviation and prevention of subsequent infections. Vaccines, including Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN)) and ACAM2000, are effective against susceptible high-risk populations. Antiviral agents like tecovirimat have also shown promising results in severe cases. Containment strategies emphasize surveillance, public awareness, and vaccination campaigns targeting at-risk groups. The emergence of monkeypox underscores the necessity for improved monitoring of zoonotic diseases and international collaboration in tackling neglected tropical diseases.

 

Author (s) Details

 

Rakesh Tank
Department of General Medicine, SHKM Government Medical College, Nuh, Haryana-122107, India.

Priyanka Tank
Department of Paediatrics, SHKM Government Medical College, Nuh, Haryana-122107, India.

 

Please see the book here:- https://doi.org/10.9734/bpi/dhrd/v6/4648

Valuation of Two Serological Tests in the Estimation of Rabies Virus Antibodies among Free-Ranging Vaccinated Dogs in Bengaluru, India | Chapter 2 | Innovations in Biological Science Vol. 4

Rabies is a zoonotic viral disease caused by an RNA virus in the genus Lyssavirus of the family Rhabdoviridae. The disease is endemic in most African and Asian countries. Globally, rabies kills tens of thousands of people annually, and domestic dogs transmit most (99%) cases. Vaccination is the practical solution for the prevention of rabies in dogs. Assessment of the immunogenicity of vaccination includes estimation of specific rabies virus neutralizing antibodies (VNA) in the target species.

We undertook a study to estimate the levels of VNA in free-roaming dogs with a history of rabies vaccination in Bengaluru city, India. We compared the rapid fluorescent focus inhibition test (RFFIT) and an in-house quantitative indirect ELISA (iELISA). The effectiveness of iELISA was evaluated using a two-tailed Spearman correlation analysis by comparing it with RFFIT. The study area comprised the jurisdiction of Bruhat Bengaluru Mahanagara Palike (BBMP), the Bengaluru civic body. The BBMP, along with several non-government organizations (NGOs), were was conducting a trap-neuter-vaccinate-release program for the prevention of dog rabies. Serum samples were collected from 250 free-roaming dogs from representative regions of BBMP, of which 125 had a VNA titre of 0.5 IU or more by the RFFIT. Furthermore, 126 dogs showed percent positivity values (PP values) more than the cut-off PP value of 57.1 by the iELISA, accounting for 50.4% of satisfactory post-vaccinal serum conversion. The sensitivity and specificity of the ELISA was 94.4% and 95.2%, respectively. Based on these data, a quantitative ELISA may be a complementary tool for sero-monitoring immune responses of free-ranging animals after rabies vaccination. The study also recommends the need for enhanced rabies surveillance for the detection of rabies occurrence as a part of the National Action Plan for Rabies Elimination (NAPRE).

Author(s) Details:

Lekshmi J. Das,
KVAFSU-CVA Rabies Diagnostic Laboratory, Department of Microbiology, Veterinary College, KVAFSU, Bengaluru 560024, India.


Please see the link here: https://stm.bookpi.org/IBS-V4/article/view/14391

Persistent SARS Infections, Malignant Evolution, and Pertinent Hindrance of Tumors by Vaccination | Chapter 7 | Current Innovations in Disease and Health Research Vol. 5

The three coronavirus variant contaminations which evolve upon severe respiratory syndromes, have infrequently been related accompanying persistence. The zealous RNA might be affected individually, or else, by new, often intrinsic, and neurological symptoms that ability represent the only disease exhibitions. At times, it may associate with changeable immunity. A persistent COVID-19 can initiate a “long COVID” scene. It has been hypothesized that, impending a protracted follow-up, the steadfastness of the SARS-CoV-2 might progress into a cancer: TMPRSS2 deoxyribonucleic acid may develop into a prostatic tumor, while ground glass lung opacities concede possibility lead to a lung tumor. In contrast, vaccines may impede the happening of a malignancy. Among these, the BCG cure predominates, together with the MMR cure; mumps and measles in the latter, being possibly being the reason for a tumor handicap. It is too early to find out a similar role for COVID-19 accompanying anti-SARS-CoV-2 vaccines, as they may have connection with cancer.

Author(s) Details:

Daniel Benharroch,
Department of Pathology, Faculty of Health Sciences, Soroka University Medical Center, Ben Gurion University of the Negev, Beer Sheva, Israel.

Please see the link here: https://stm.bookpi.org/CIDHR-V5/article/view/11588

Is It the End of the COVID-19 Global Public Health Emergency? | Chapter 6 | Current Innovations in Disease and Health Research Vol. 4

 The SARS-CoV-2 bug has been a indiscriminate our daily lives since allure inception towards the concluding part of 2019. The worldwide journey throughout the pandemic has existed one of many steps in progression and steps in reversion and can be described as a swell-coaster like ride. Phase 4 of the SARS-CoV-2 universal is currently moving the majority of the world's people. Phase 4 entails preparation for future pandemics and outbreaks and making loans in infrastructure development and more research. The most persuasive tool being used to hold and eventually stop the global universal is the ongoing worldwide COVID-19 vaccination programmes and the supporter doses provided therein. According to the WHO the total newspaper COVID cases have been abating on a constant scale accompanying the latest (8 of June 2023) reported a newspaper update describing a deficit of 300,000 cases (an 38% decline from the previous weekly enumerations). In contrast to the positive course of movement of COVID cases on a statement basis, The United Kingdom’s cases seem expected regressing. With the onset of new waves of contamination in many countries because mid-2020 and the emergence of variations, governments are confronted to the restricted ability to series policy action.  Although the overall COVID picture is very bright, the world's society should not be calmed into a false sense of security cause, as happened accompanying the Omicron variant in December 2021, the world has visualized firsthand what the discovery of a new variant able and usually willing to change to infection rates in addition to the global monetary and fiscal markets. The COVID-19 pandemic is in allure final stages; nevertheless, a continued and orchestrated worldwide effort is relevant to ensuring that the universal is truly ended what no unexpected spread ups happen. The development of vaccines against COVID-19 has been remarkably rapid, accompanying less than individual year elapsing between the sequencing of the novel circulating quickly genome and the commencement of main vaccination campaigns indifferent parts of the globe. The single excellent threat to doubtlessly ending this current universal is the premature declaration to it being over. It is immediately high time for the consolidation of the global healthcare materials, systems, governments and key stakeholders to address the antivaccination campaigners in a united manner in consideration of bring an conclusion to the discourse and misunderstanding between two together camps. It is only through global merger and collaboration that this cycle can be drawn to an end. On the 5th of May 2023 the Chief of the World strength organization, actively and with excellent optimism declared that COVID-19 was not any more a public health crisis. It was however emphasized that the disease still poses a danger what measures and cautions should still be prioritized for fear that the virus from spreading.

Author(s) Details:

Jared Robinson,
Sir Seewoosagur Ramgoolam Medical College, Belle Rive, Mauritius.

Indrajit Banerjee,
Department of Pharmacology, Sir Seewoosagur Ramgoolam Medical College, Belle Rive, Mauritius.

Please see the link here: https://stm.bookpi.org/CIDHR-V4/article/view/11449

The Perceptions and Acceptance of Covid 19 Vaccination among Health Care Workers in Northern India| Chapter 4 | Current Overview on Disease and Health Research Vol. 7

 Since the start of the period 2020, the Covid 19 contamination has become the most considerable ordeal for the complete humankind, particularly for healing pros and added members of the approximate community. The conclusion to prioritise vaccines for HCWs and FLWs will boost warrior self-esteem and essence from now on. This study was a preliminary attempt to recognize and address any cure doubt determinants among HCWs. Although principal part had enlisted for immunization, the plurality of HCWs had limited information of the cure on account of the recent cure rollout and the lack of particularized research verdicts. All measures must stop living, including exhaustive IEC projects proposed at HCWs and the general public on a orderly action, to develop vaccine information. In an term of misreport, a powerful communication tactics is very urged, as social publishing plays an main function in extended both real and wrong ideas, jeopardising the entire gains of profitable immunization and herd privilege. HCWs to present image of role models for the society and inmates, growing vaccine agreement with ruling class.

Author(s) Details:

Ravishekar N. Hiremath,
Department of Community Medicine, AFMS, New Delhi, India.

Kasi Viswanath,
Department of Community Medicine, AFMS, New Delhi, India.

S. R. Manjunath,
Department of Community Medicine, AFMS, New Delhi, India.

Sandhya Ghodke,
Department of Anaesthesia, Rainbow Children’s Hospital, Bangalore, India.

Please see the link here: https://stm.bookpi.org/CODHR-V7/article/view/9432

Impact of Health Education on Parents’ Knowledge and Attitudes Regarding Vaccination at Mouanko, Edea Health District, Cameroon | Chapter 9 | Current Overview on Disease and Health Research Vol. 8

 Background: Vaccination is popular to prevent 2.5 heap deaths done yearly worldwide. However, immunization coverage in Sub-Saharan Africa containing Cameroon is still low due to weak knowledge on immunization.Objective: We aimed at fact-finding the impact of health instruction on parents’ information and attitudes concerning vaccination.Methods: This was a cross localized interventional study which examined the impact of health instruction on parents’ knowledge and stances regarding immunization in the Mouanko Health Area. Participants were selected utilizing the cluster sampling method and were randomly appointed either to an intervention or a control group. The attack was health instruction on vaccination that was executed only to the intervention group after executing a pretest. Data on knowledge and stances was collected utilizing a semi-organized questionnaire. Each correct answer to questions on the questionnaire was likely a point. The knowledge division was scored on 13 and persons who succeed seven points and above were termed knowledgeable while shareholders who cut four points and above on seven were said to have beneficial attitudes. Data was composed from May 13 to June 15, 2019 and analysed using SPSS tale 25.0.  Results: Out of the 270 parents the one participated in the study women were the most depicted (88.9%). Their mean age was 25.4 (SD = 3.9) years and categorized from <21 years (22.2%) to >40 years (11.1%). More than half (53.7%) of the colleagues’ children were in the old range 0 – 6 months. Most of the participants (66.7 %) were wedded, 74.0% had first school and 72.2% had an average monthly revenue of less than 37, 000frs CFA. More than half (61.1%) of the members lived about 5km and more from the immunization centre. Up to 70.0% of the participants had perceived about vaccination, but only 25.0% saw its benefits. Less than half (40.7%) had definite feelings about vaccination.After the mediation, there was a important increase in the proportion of partners who had information on vaccination from 35.0% to 57.6% and from 31.0% to 41.9% for certain attitudes. The p-principles were at 0.001 and 0.012 for knowledge and stances respectively (CI = 95%).Conclusion: The definite change in the intervention group after the invasion indicated the cost-influence of the health instruction.

Author(s) Details:

Enow Vivian Ayamba Eta,
Department of Nursing, Faculty of Health Sciences, University of Buea, BP63 Buea, Cameroon.

Eric Ngala,
Department of Nursing, Faculty of Health Sciences, University of Buea, BP63 Buea, Cameroon.

Thomas Etamba Eta,
Government Bilingual High School Tiko, P.M.B. 00 Tiko, Cameroon.

Gregory Edie Halle Ekane,
Department of Obstetrics and Gynaecology, Faculty of Health Sciences, University of Buea, BP63 Buea, Cameroon.

Please see the link here: https://stm.bookpi.org/CODHR-V8/article/view/9033

Conspiracy Beliefs of COVID-19 Vaccination in Ghana| Chapter 6 | Research Developments in Science and Technology Vol.4

The purpose of this inquiry was to check into Ghanaians' opinions of COVID-19 vaccination conspiracy theories. The extremely contagious SARS-CoV-2 virus spread internationally in a short amount of time. Most Ghanaians who believe in science and the COVID-19 vaccine's success in stopping the spread of the corona virus disease have received vaccinations and are keen to urge others to do so as well. Others disagree with the existence of the virus and the vaccine's severe adverse effects if they take it. The COVID-19 vaccine, like other vaccines designed to prevent certain illnesses, has generated a wide range of responses. The outcomes of the study demonstrate that COVID-19 vaccine conspiracy theories are not generally embraced in Ghana.

Author(s) Details:

Gloria Ahima Baffoe,
Department of Communication and Media Studies, University of Education, Winneba, Ghana.

Naa Korkor Leeyoo Watson Nortey,
Department of Communication and Media Studies, University of Education, Winneba, Ghana.

Please see the link here: https://stm.bookpi.org/RDST-V4/article/view/6854

A Review on Xenobiotics: The Impact of SARS-CoV-2 on the Evolutionary Development of Human | Chapter 06 | Issues and Development in Health Research Vol. 6

This is a topic that will be discussed in the analytical section of this article, where South Africans' priorities for HIV/AIDS and health will be compared. This study examines the characteristics that predicted respondents' selection of HIV/AIDS as an important issue for the government to solve using data from the Fourth Round of the Afrobarometer survey in South Africa. The study's dependent variable was the identification of HIV/AIDS as a significant governmental issue. Other possibly key factors included respondents' personal knowledge of HIV/AIDS, such as knowing someone who died of AIDS, poverty, and their perceptions of the government's response to the HIV/AIDS issue. A logistic regression analysis took into account the respondent's background and demographic information. The findings revealed three characteristics that influenced respondent choice of HIV/AIDS: race, particularly being a Black South African, government prioritisation of health, and the rural-urban divide. The conclusion was that advertising aimed at mobilising public support for comprehensive HIV/AIDS solutions in South Africa should focus on HIV/AIDS rather than health.

Author(S) Details

A. Vladyko
Republican Scientific and Practical Center for Epidemiology and Microbiology, Minsk, Belarus.

E. Fomina
Republican Scientific and Practical Center for Epidemiology and Microbiology, Minsk, Belarus.

P. Semizhon
Republican Scientific and Practical Center for Epidemiology and Microbiology, Minsk, Belarus.

View Book:- https://stm.bookpi.org/IDHR-V6/article/view/4246

Living with Sars-Cov-2 Variants. An Update in the Pandemic Era | Book Publisher International

 SARS-CoV-2/COVID-19 is wreaking havoc on health systems and economics all over the world. In recent months, genomic analysis of pandemic SARS-CoV-2 isolates revealed viral variations that are less sensitive to neutralisation by convalescent plasma, vaccine-elicited plasma/sera, or SARS-CoV-2 monoclonal antibodies than previous SARS-CoV-2 strains. The emergence and spread of SARS-CoV-2 variants that evade vaccine immunity would be a cataclysmic development for a world expecting relief from the pandemic and a return to normalcy, as these could result in new infections in vaccinated people and those who have recovered from coronavirus disease 2019. (COVID-19). SARS-CoV-2 is an RNA virus (a family with a long history of adaptive evolution).

Autho(s) Details

Dr. L. E. Weimer
National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.

G. Cattari
Reparto COVID, Ospedale Marino-Alghero, ASSL Sassari, ATS Sardegna, Italy.

A. Binelli
National Center for Global Health, Istituto Superiore di Sanità, Rome, Italy.

E. Fanales Belasio
Department of Infectious Diseases, DMI, Istituto Superiore di Sanità, Rome, Italy.

S. Piras
Reparto COVID, Ospedale Marino-Alghero, ASSL Sassari, ATS Sardegna, Italy.

F. Sensi
Direzione ASSL Sassari, ATS Sardegna, Italy.

View Book:- https://stm.bookpi.org/LSCVUPE/issue/view/272

A Novel Approach on Immunization by Replication- Competent, Controlled Viral Pathogen: Exploring for Diseases Refractory to Effective Conventional Vaccination? |Chapter 4| Current Topics in Medicine and Medical Research Vol. 8

 The first vaccine that targeted small pox in 1796 was studied by Edward Jenner. Overall, for disease prevention, vaccination has been a very good method. However, illnesses and disorders that can not be successfully avoided or treated by vaccines still occur more than two centuries after the first use of the vaccine. Unfortunately, global diseases, including influenza / flu, tuberculosis , malaria, HIV / AIDS, and oral and genital herpes, are diseases that have remained refractory to vaccination or are insufficiently protected against by vaccination. Although efforts to develop vaccines based on the "classical" model (described below) continue, it may also be necessary to consider novel approaches that may have the potential to induce superior immune responses qualitatively and/or quantitatively.

Our failure to recognise the molecular basis of current liveattenuated vaccine attenuation and immunogenicity is a key constraint in the development of novel vaccines against today and tomorrow's challenging infectious diseases. This is partly due to the empirical existence of their growth [1,2]. The majority of vaccines currently approved are either subunit vaccines (comprising isolated proteins or protein fractions) or attenuated types of microorganisms that cause disease. Pathogens are attenuated by their killing or by hereditary deficiency of their replicative ability. Although attenuation provides the protection needed, the ability of so-modified pathogens to induce robust inflammatory responses is almost universally compromised, which translates into suboptimal humoral and T-cell responses[3-6]. The comparison of immune responses elicited by a wild type pathogenic agent vs. those caused by an attenuated agent is obviously not feasible. Many studies, however, contrasted immune responses elicited by viral vectors that were attenuated but retained residual capacity to replicate and corresponding vectors that were incompetent for replication[7-10]. Results showed that attenuated viruses retaining some replication capacity induced immune responses that were more complete and more potent than non-replicating comparison viruses.

On the basis of these considerations and observations, we hypothesised that a genetically engineered viral pathogen that can be triggered transiently in an inoculation site region to (local) replicate will be a superior immunisation agent to a traditional vaccine with an efficiency approaching that of the corresponding wild type agent[11]. Here, replication is understood as agent propagation. Bramson[12] endorsed that full immune response can be obtained from immunisation with a disease-causing virus modified to subject replication-essential genes to the control of a non-lethal heat-activated gene switch in the presence of a drug-like compound.

How does one restrict a viral pathogen's replication to the area of the inoculation site as well as limit the length of its replication? It is well known that in the area in which they have been administered, viruses will not live, but will disperse inside the host organism. Therefore, in the inoculation site region but not elsewhere, an appropriate control mechanism will need to be capable of activating replication. It is believed that a physical "signal" that can be targeted at the inoculation site region will need to be responded to by such a control mechanism. The use of a highly heat-inducible heat shock protein gene (HSP) promoter to regulate the expression of replication-essential genes of a pathogenic virus is one possibility, representing perhaps the only possible solution available at this time. Some HSP promoters, such as the human HSP70B promoter, have very low basal activity, which can be induced by heat activation several thousand times [13,14]. Rohmer et al.[15] have produced novel gene transfer vectors for adenovirus that feature enhanced and strict control of transgene expression using promoter insulation from the HSP70B promoter. For gene therapy applications benefiting from external regulation of therapeutic gene expression or combination therapy with hyperthermia, these vectors have potential[16]. In all mammalian cell types, the promoters appear to be capable of being activated. A heat dose that is basically beyond the physiological range but can be easily tolerated by a human subject (44-450C for 5-10min) involves activation of the HSP70B promoter. If this is needed, the promoter could be changed so that it reacts to a lower heat dose[17]. In several ways, heat can be targeted. A simple and robust solution will include applying a heating pack in the case of intradermal or subcutaneous inoculation. Using well-known and inexpensive technology (of the kind used in commercial products such as ThermaCare), such a pack may be manufactured.

Safety from accidental transient activation or, worse, run-away activation will be the most critical problem with an immunisation agent that can be activated to replicate with near-wild type efficiency. The mode of regulation of HSP promoters emerges from a practical (not safety-related) issue that also needs to be answered. Exposure of a cell to heat (even prolonged heat) results in a heat shock transcription factor 1 (HSF1) transient activation that then binds to and mediates HSP promoter transcription. Within a few hours of heat activation at most, HSF1 returns to an inactive form. As a result, HSP promoters per se are not well suited to the control of a pathogen 's genes whose operation is required during most of the replication cycle or which need to be active at different cycle times. It has been suggested that adequate safety from inadvertent activation, whether due to exceptional circumstances ( e.g. ischemia, intoxication, etc.) or recombination events, could result from the use of a dual-responsive gene switch to control at least two viral pathogen replication-essential genes to be used as immunisation agents[11]. Dual-responsive gene switches activated by a combination of heat and a small-molecule regulator (SMR) have been previously described and are known to strictly control both in vitro and in vivo target gene expression [18-20]. The gene switches consist of I an SMR-activated transactivator expressed from a heat- and transactivator-activated promoter cassette, and (ii) a transactivator-responsive promoter to drive a gene of interest. Fig. represents a viral pathogen with two replication-essential genes controlled by a dual-responsive gene switch. 1A, and how the gene switch functions is shown in Fig. 1B. Upon administration to a selected inoculation region of such a replication-competent regulated pathogen, replication of the agent is activated by localised heat treatment, e.g. the application of a heating pack, in the presence of SMR. The SMR may be systemically administered or can be co-administered with the immunising agent. In the infected cells, the triggered gene switch will remain active until clearance of the SMR has occurred or the replicating agent has lysed the cells. The agent is safely disabled thereafter. Intentional re-activation of replication would be possible for as long as the agent remains in the inoculation zone.

Is building such replication-competent regulated viruses feasible? Are they likely to cause better immune reactions than traditional vaccines? We placed under the control of a dual-responsive gene switch (manuscript in preparation *) two replication-essential genes of a wild type strain of Herpes Simplex Virus 1 ( HSV-1). Antiprogestin mifepristone and closely related compounds (but not progestins) were activated by the transactivator incorporated in the latter gene switch. In vitro, in the presence of antiprogestin, the recombinant virus replicated nearly as effectively as the wild-type virus after heat activation, but not in the absence of either antiprogestin or heat treatment. In the mouse, replication of the virus was also rigorously regulated. The once-activated recombinant virus was substantially more protective than the corresponding non-replicating virus in immunisation / challenge experiments. These results encourage and require an examination of the full potential of the proposed approach to immunisation.

Agent                                                                                                                      Potential use

HSV * regulated by replication-competent                                           Therapeutic or preventive                                                                                                                       immunisation toward Oncolytic                                                                                                                       Treatment HSV

HSV * regulated by replication-competent                                          Anti-HIV / AIDS immunisation, flu, Heterologous antigens are expressed (e.g., from                               Via tuberculosis, etc.   HIV, the flu, M. tuberculosis)

Replication-competent HSV controlled * +                                          Immunization against the infectious pathogen co-infecting the virus                                                     (e.g. adenovirus, papilloma, polyoma, infecting bacterial pathogens that contain at                                               other herpesvirus etc.)  least one viral pathogen   The replication-essential gene that is regulated by the  The transfer of dual-responsive genes (present in the HSV that is controlled)

Replication-competent regulated HSV *                                                Immunization against the viral pathogen expressing a replication-essential gene                                                 co-infecting (basically any viral pathogen       of a viral pathogen co-infecting under gene                                          capable of co-infection)                      switch  regulation + viral pathogen co-infecting with disabled  replication-essential genetic control

How broadly will this technology be applied? Only if the pathogen normally engages the host transcriptional machinery for the expression of its genes can replication of a viral pathogen be regulated by the above-described dual-responsive gene shift. At first sight, this limitation is less significant than one would expect (Table 1). There has been a long history of the use of viral vectors (replication-defective and attenuated) to express heterologous antigens [21,22]. As a potent immunisation platform, a replication-competent regulated virus can serve. Expression of heterologous antigens in the sense of vigorous viral replication is expected to result in superior immune responses for the reasons which were addressed at the beginning of this correspondence. In addition, via complementation, viral pathogens that do not use the host transcriptional machinery can be regulated. A replication-essential gene of such a virus and a co-infecting (replication-disabled or replication-competent-controlled) virus that expresses the replication-essential gene under the control of a dual-responsive gene switch can disable the gene product of such a virus. It is noted that if viral vectors are used as immunisation or oncolytic agents, the issue arises as to whether the effectiveness of these agents would be significantly diminished by pre-existing immunity. For HSV, our preferred backbone for managed virus construction, several studies have addressed this problem (cited in ref.9). The prevailing answer is that pre-existing immunity has little or only relatively minor effects on the immune response to antigens delivered by HSV or on the oncolytic HSV anti-tumor efficacy.

Author(s) Details

Richard Voellmy

Department of Physiological Sciences, University of Florida College of Veterinary Sciences, Gainesville, FL, USA and HSF Pharmaceuticals SA, La Tour-de-Peilz, Switzerland.

David C. Bloom
Department of Molecular Genetics & Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.

Nuria Vilaboa
Hospital Universitario La Paz-IdiPAZ, Madrid, Spain and CIBER de Bioingenieria, Biomateriales y Nanomedicina, CIBER-BBN, Spain.

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