# Impact of Veterinary Vaccines on Human Health and Probable Challenges

Md Mehadi Hasan Sohag, Yahia Chebloune

► To cite this version:

Md Mehadi Hasan Sohag, Yahia Chebloune. Impact of Veterinary Vaccines on Human Health and Probable Challenges. Acta Veterinaria Eurasia, 2021, 47 (3), pp.197 - 200. 10.5152/ac-tavet.2021.21005. hal-03471346

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Submitted on 8 Dec 2021

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# Impact of Veterinary Vaccines on Human Health and Probable Challenges

Md. Mehadi Hasan SOHAG<fnref n="1" />,<fnref n="2" /> ID, Yahia CHEBLOUNE<fnref n="3" /> ID

Cite this article as: Sohag, M. M. H., & Chebloune, Y. (2021). Impact of veterinary vaccines on human health and probable challenges. *Acta Veterinaria Eurasia*, 47, 197–200.

ORCID iDs of the authors: M.H.S. 0000-0001-6058-1626; Y.C. 0000-0001-9179-6486

## Abstract

Like antibiotics, extensive uncontrolled use of veterinary vaccines might be a threat to human health in occupational livestock production and subsequently in animal food product consumption. Although veterinary vaccines are necessary to control a large variety of infectious diseases in animals, risk assessment, rules, and regulations are highly justified for the sake of human health and safety. Indeed, during the last century, there have been significant changes in livestock production due to the increasing demand for animal products, and these changes have dramatically augmented the occupational exposure of humans to animals. To prevent risks

of cross-reactions of veterinary vaccines in humans, strict guidelines are now followed, in every step of vaccine production and people are aware of the consequences. Besides this, systemic biology approaches are also being explored to determine host-pathogen relationships. This mini-review examines some of the scientific bases of this type of risk in the era of systemic medicine, as well as the efficacy or inadequacy of preventive regulations.

**Keywords:** Cross-reactions, host-pathogen relationship, human health, veterinary vaccine

## Introduction

Vaccination is the most common method intended to train the animal or human body to efficiently fight against infectious diseases before infection sets in, and it helps to eradicate contagious diseases (Pastoret, 2010). The best example is of the eradication of the deadly smallpox in the human population worldwide, using the naturally attenuated cowpox virus (vaccinia) as an immunogen to vaccinate humans (Parrino & Graham, 2006). Veterinary vaccines are used frequently to protect animals against a variety of infectious diseases. These are formulated for animal use only and are not used to vaccinate humans (Roth, 2011). However, cross-reaction cannot be ruled out when handling or caring for animals or when processing animal-derived foodstuff (Berkelman, 2003). Although most veterinary vaccines are based on inactivated formulations, there are still over 500 licensed veterinary formulations based on live vaccines. Though it is not crystal clear whether veterinary

medicines has a significant effect on humans because routine surveillance has not been performed, some incidents have been evidenced (Berkelman, 2003). The increase in the number of live vaccines and their increasing use in animals pose a higher risk for the safety of human exposure to cross-species infections. Although these live vaccines are designed to be non-pathogenic in animals, they may retain or revert to pathogenicity following cross-species infection in humans. The low-pathogenic avian influenza (LPAI) vaccine is a good example till date (Lee et al., 2012). In addition, human exposure to an increased number of animals vaccinated with a variety of live vaccines may result in multiple infections with different vaccines that could generate recombinant pathogenic viruses in humans. These risks are further increased in elderly persons who are immunosuppressed due to age or in patients using immunosuppressive drugs following transplant or as treatment against inflammatory diseases. Contaminant mammalian infectious endogenous retroviruses (ERV) may also cause

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<footnote n="1">¹Department of Genetic Engineering and Biotechnology, Jagannath University, Dhaka, Bangladesh</footnote>

<footnote n="2">²Biotechnology Research Initiative for Sustainable Development, Dhaka, Bangladesh</footnote>

<footnote n="3">³INRA/UGA USC 1450, Pathogenesis and Lentivirus Vaccination Laboratory, PAVAL Lab., Université Grenoble Alpes, Grenoble Cedex, Rhône-Alpes, France</footnote>
co-infections of viral vaccines with potentially zoonotic viruses when injected (Dewannieux et al., 2010). There is an increased demand not only to produce safer veterinary vaccines but also vaccines that meet the concept of One Health (Francis, 2017).

To test the safety and efficacy of the veterinary vaccines and the possibility of cross-reaction with humans, the EU and the USA have defined their regulations and guidelines. They have stringent regulatory frameworks to test vaccines and to evaluate the safety and efficacy of vaccines that are meant exclusively for animal use (Bruckner, 2010; Fisher, 2014; Sheridan & Coughlin, 2010).

System biology would be the best option to analyze the detection, prediction, and reduction of the risks of zoonotic diseases in humans. Investigation of host-pathogen relationships (Interactome) by a computational systemic approach may yield potential veterinary vaccines devoid of the risk of cross-reactions (Adams et al., 2011).

## Strategy and Outcomes

For reverse transcription, the genome of mammals has a high load of retroviral element that could be infectious due to the endogenous retroviral protein (ERP). Strong similarities between ERV and present-day retrovirus show a close phylogenetic relationship. Hence, ERV is linked to the possible consequences of contamination in vaccine production (Miyazawa, 2010). In most mammals, more than 40% of genomes are identified that can replicate with a wide copy number and are classified into two major classes. Class 1 includes the interspersed nuclear element (long and short), while class 2 incorporates the LTR (Long Terminal Repeat) or ERV, which may or may not contain an envelope protein (Hayes et al., 2013).

ERP comprises about 8-10% of the host genome (mammals) and contains many proviruses (Ishida et al., 2015). There is proximity in the LTR elements of mammals, but these elements are distant in non-mammals (Hayes et al., 2013). This implies that they have the same ancestor, and that there is a genetic link between ERV and infectious retrovirus (Hayes et al., 2013). From this point of view, it can be hypothesized that the infectious retrovirus first infected a virus-cell, and the viral particle accessed the germline and was transmitted in a simple Mendelian manner. For example, the koala retrovirus (KoRV), in the first stage of endogenization, has two forms—infectious and endogenous. Over time, it loses pathogenic properties and adapts to the host (Ishida et al., 2015). ERV can also modify some signals and produce some retroviral proteins like oncogenes which are noxious for further vaccine production (Dewannieux et al., 2010). Besides this, a recent report shows that human endogenous retroviruses (HERVs) expressed in tumor cells are not compatible as vaccine targets (Denner, 2021). However, the efficacy and safety of the use of HERVs expressed from tumor cells as retroviral vaccine preparations is also suggested by other scientists (Bermejo et al., 2021).

In the case of Brucellosis, 4-5 million doses of live bacterial strain were administered as vaccines, and a minute amount was found in human exposure, though there was also a risk for at least 8000 unintentional needle sticks. In the case of vaccinia, the modified live rabies virus is used as vaccine and has been administered in more than 22 million doses as oral bait, but in one instance, a 26-year-old pregnant woman experienced severe health problems due to exposure; however, she was treated early and gave birth to a boy without infection (Berkelman, 2003).

The major concern of the study is that the occupational exposures to vaccines can occur through used needles. Some shreds of evidence of necrosis were found when veterinary technicians handled vaccines containing *Salmonella enterica*; similar situations also arise in the case of those who are occupationally exposed to aquaculture vaccines (Berkelman, 2003). There are strict guidelines defined by the EU and the USA to standardize vaccine production at every stage.

According to these guidelines, detailed studies have been conducted, and monographs exist for every aspect of production. Any material that is used must be inactivated. There are deep concerns regarding bovine serum (BS) used as medium for BVD (Bovine Viral Diarrhea) virus (used after test and validated) (Polak et al., 2016). The seed lot system is also governed, as the master seeds remain in minimal use and the master seed is also tested. The embryonated egg is taken from specific pathogen-free (SPF) chicken flocks and tested, and the cell line is tested for determining cytopathic effects and the presence of influenza viruses or other viruses (Brauer & Chen, 2015). However, alternative testing and analysis, like the nucleic acid amplification technique, is applied to antiserum to neutralize the vaccine virus (Bruckner, 2010).

Moreover, safety tests begin from the cell bank to virus seed and to substances of viral origin. For initial cultures, a detector cell line is chosen based on the sensitivity of the virus (Wisher, 2002). Then it is tested to examine the cytopathic effect (CPE) using hemadsorption assay (HA), immune fluorescence Assay (IFA), and others. The EU and the USA have formulated guidelines to examine how the pre-clinical safety is tested in vaccine preparation. For preparing virus monolayer seed culture, neutralization is ensured to prevent infection and propagation of the virus seed in the detector cell (Gombold et al., 2014).

These procedures are followed by the endpoint test. Cytopathic viruses display CPE or morphological changes that indicate viral contamination, and this is the best technique that confirms particular antigens in particular cell cultures (Sheridan & Coughlin, 2010). Incremental system biology, especially the "Interactome" modeling concept, comprises the tools of vaccine immunotherapeutic development, as this approach might be used in simulation which can guide vaccine development
and the selection of immunotherapeutic drug candidates (Kuleš et al., 2016). A dynamic Bayesian network is used to determine the model called the BioSignature Discovery System (BioSignatureDSTM), based on machine learning and pattern recognition (Baurley et al., 2018). This computational strategy depicts scores and relationships between genes on the pathway instead of a single gene (Azuaje et al., 2011). Gene Ontology (GO) categories and the simulation process are used for modeling the disease or condition, using BioSignatureDSTM. Additionally, proteomic data can easily be integrated into the model, ensuring the presence and pattern of protein-encoding genes responsible for the diseases (Adams et al., 2011).

The microbiome has greater ability to infect the host cell. Viruses and bacteria endemic in the body are constantly interacting among themselves in a complex and dynamic process from infancy through adulthood. Though the viral epigenetic phenomenon is not well established yet, the phenomena of viral mutation and recombination occur and scientists do not understand how viruses and genes interact. Thus, it is clear that what is not recognized about the effects of extensive use of live virus vaccines on human health is far greater than what is known. Vaccine recommendations now direct doctors to vaccinate persons with a low and high level of immune suppression, including organ transplant recipients; those diagnosed with HIV, cancer, and primary immune deficiency disorders, those with autoimmune and chronic inflammatory disorders such as lupus, rheumatoid arthritis, multiple sclerosis, and vasculitis (Fisher, 2014).

There is evidence of risk in using primary monkey kidney cells for preparing vaccines because monkey cells can be infected with SV40 (and with other monkey viruses). Genetically modified influenza virus-vectored vaccines, rotavirus, baculovirus, Newcastle disease virus, parainfluenza virus 5, poxvirus, and so on are highly communicable. One of the major concerns is that the live rubella vaccine virus can be transmitted through breast milk. The chickenpox vaccine can cause vaccine strain infection. The shingles vaccine can cause varicella-like lesions, but there are recommendations that exposure does not equal illness (Fisher, 2014).

Some unintentional and non-occupational exposures show vague evidence of infection. However, problems arise when an individual is intentionally using the animal vaccine on themselves. There are some misconception and misuse in this regard among people who cannot afford to buy vaccines for themselves and use animal replacements instead (Berkelman, 2003). More than 30 infections have been identified in the last 25 years, most of them with a zoonotic origin. Thus, there is concrete evidence for the hypothesis that infectious agents can jump the species barrier. An example is the poultry vaccine produced in duck cells contaminated by adenovirus, which leads to egg drop syndrome in poultry (Pastoret, 2010).

## Conclusions and Recommendations

Though it is not clearly understood, it is evident that veterinary medicine has a profound effect on humans, and surveillance has not been routinely performed. For regulation of the process, the U.S. Food and Drug Administration (FDA) has set some guidelines to test issues of safety and efficacy of vaccines (a major concern in vaccine research) and to determine contamination by other infectious agents. As the use of veterinary vaccines rapidly increases, we must be aware of human exposure and be conscious of its adverse effects. We should scrutinize the master cell banks that are genetically modified, the purity of starting materials and end products, follow good manufacturing practices, and ensure validation of inactivation processes. The need to use the system biology approach to identify the host-pathogen challenge is also evident.

**Peer Review:** Externally peer-reviewed.

**Author Contributions:** Concept – M.M.H.S., Y.C.; Design – M.M.H.S., Y.C.; Supervision – Y.C.; Resources – Y.C.; Materials – M.M.H.S.; Data Collection and/or Processing – M.M.H.S.; Literature Search – M.M.H.S., Y.C.; Writing Manuscript – M.M.H.S., Y.C.

**Conflict of Interest:** The authors have no conflicts of interest to declare.

**Financial Disclosure:** The authors declared that this study has received no financial support.

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