An Insight towards the Role of Micro-Biota in Vaccine Development for COVID-19
The whole world is moving around to fight against corona virus (Covid19). In this present scenario, the study of gut-microbiota with vaccine development is studied. And it is tried to understand the role of gut microbiota in the immune response to the host. It is found that the diet is taken by the person of age, sex; patients will play a significant role in gut microbiota and show immune response towards vaccines. Many modern technologies of bioinformatics are applied to understand the diversity among gut microbiota with respect to age, sex, patients to immunity. It is recommended that these analyses will help to improve vaccine development against COVID19.
Introduction
Coronavirus, the big giant started eating all the humans from all over the world. It got its name COVID19 due to coronavirus originated in the year 2019. As it is moving from Wuhan to all over the world slowly but gradually. As it is one and first kind of virus which goes host body through touch or sneezing from an infected person basically having lung infection, becoming the world’s largest killing disease [1]. Hence, scientists, researchers all over the world have now started the trials of the potential vaccine candidates to kill coronavirus. In this present scenario, the author makes an effort to take the opportunity to study the relationship between gut microbiota and vaccine development for covid19.
Microbiota and Vaccine Response
The microbiota constitutes a large and diverse group of micro- organisms. This microbiota performs essential functions including the nutrients metabolism, gut homeostasis maintenance, regulation of gut mucosal immunity, etc. Studies show that the profound effect of drugs may change the microbiota composition which leads to the consequences in metabolism and immune responses [2, 3] of T-helper cells [4].
Vaccination reduces the disease progression burden in the world as it is safe and vaccine has no side effects. A vaccine characteristic includes:
- Vaccine formulation- it includes vaccine delivery systems, adjutants, and immunomodulators.
- Nature of antigen- it includes whole microbes, purified protein, polysaccharide, and nucleic acid.
- The dose: how much quantity is used for children, adults, and so on.
- The route of immunization- either it would be parental or mucosal.
- Vaccine schedule: what will be the vaccine schedule either homologous or heterologous prime-boost strategies,
- Time for vaccine doses- this includes gapping between vaccine doses if the boosting dose is there.
A vaccine induces B-cells to produce antigen-specific antibodies which can be booster doses as required for a specific disease. Studies confirmed that if intestinal flora is not well flourished then inflammation and blunted immune response are observed [5, 6]. In the developing world it is observed that due to poor sanitation, most of the vaccines get failed. This is associated with child growth with cognitive deficits [7].
This gut microbiota shows the reduced or absent population of certain commensal flora or overgrowth of microbes like Bifidobacteria, Lactobacillus, and Butyrate- producing Clostridia allows immune dysregulation of Bacteroides and Proteobacteria have an overgrowth [8]. Autoimmunity is regulated by gut microbiota [8] and immunity becomes hyperactive. The gut-brain axis is well studied which includes a connection between the vagus nerve, blood-brain barrier, lymphatic system, and newly discovered glymphatic system.
In recent years, it was shown that microbiota plays a significant role in the immune response to injectable and oral vaccines [9]. As soon as vaccination started during the birth of an individual, immune response and microbial community started developing. There is evidence that shows microbiota shows the immune response in both pre-clinical and clinical studies [10].
This microbial mutual relationship plays a critical role in the body’s normal functions and maintaining homeostasis. Microbiota continues its work of modulating host immune functions after every vaccine doses. If microbial stimulation is not working there will be misbalanced in the intestinal immune system, i.e. the immune system will not work anatomically and functionally. Basically it is seen IgA and intraepithelial lymphocytes show improper balance in GFmice and more examples are studied [11].
Animal Model for Vaccine Development
Gnotobiotic animal models are the one best example to study gut microbiota on host responses towards vaccines [12]. Gunny pig model studies the effects of probiotics on the gut microbiome composition during human rotavirus (HRV) infection. This resembles human infant donors, so the study is easy to understand the immune response of vaccines in children. Gn models also studied to better understand gut dysbiosis [13, 14, 15, 16, 17, 18, 19]. Since pigs are similar to humans in physiologically, anatomically, and immunologically, they are chosen as a good animal model that is used in organ transplant [20]. It is recommended that Guinea pigs will be tested against childhood vaccines like Hepatitis B for being a success which requires microbiota like high proteobacteria, high Bacteroides, reduced or absent Bifidobacteria and lactobacillus, high or protective strains of Clostridia, healthy HGM.
Microbiota will play a continuous source of natural adjuvant which controls innate and adaptive immunity [21]. This endogenous adjuvant potential is being an inactivated influenza vaccine that showed that GF or antibiotic-treated mice had shown significant response [22]. This shows a strong correlation between the expression of TLR5 and the magnitude of the antibody response.
Diet and Microbiota
Nutritious diet directly interacts with microbes to promote or inhibit their growth. Dietary resources make our intestinal bacteria work more properly and efficiently [23, 24]. Hence there would be a direct and indirect effect of diet in the microbiota. The nutrients also help in the protective functions of the intestinal barrier in many ways. This will affect the host-microbe interface and dysbiosis occurs.
Covid19 pandemic is the world’s largest threatening disease in 2020. Everywhere in the world scientists are trying to combat the disease which appears more challenging. As soon as we understand the mechanism it is better to prepare a vaccine. The presence of SARSCov2 RNA in the stool of some patients and diarrhea suggests that there would be a connection joining the lung and the intestine. It is said that most of the asymptomatic children and adults may shed infectious virus particles in the stool leading to infection in others. The diverse nature of gut microbiota and other necessary microbes in the gut might be playing a significant act in describing the COVID19 disease. The immune- compromised patients mostly elders and patients with type- 2 diabetes, cardiovascular disorders play fairly in fighting covid19. A very interesting fact is observed in murine models is that removal of certain gut bacteria by antibiotic leads to increased susceptibility to influenza virus infection in the lungs [25].
Prebiotics/Probiotics
Prebiotic agents are identified and tested in both mice and humans for their capacity to modulate the microbiota for host benefits. For example, whole grains and brown rice improved fecal bacterial diversity increased the firmicutes: Bacteroides ratio [26]. Sometimes medical practices also recommend prebiotics, implying to a microbiota-dependent mechanism for its anti-diabetic properties.
Since gut microbiota is ductile and very easily molded by diet, it can be said that personalized diet strategies could be implemented as a supplementary diet. Most important is that gut microbiota profiling in each and every patient by giving effective and recommended diet specialized with pre/probiotics such as fructooligosaccahride (FOS), galactooligosaccaherides (GOS), and various lactobacilli strains to improve gut dysbiosis, which will improve the immune response of patients. It is seen that the lung-gut story will work for SARS-CoV-2 infection as most of the patients have respiratory symptoms. It is observed that all the probiotics are not the same, Lactobacilli and Bifidobacteria are the only two types of non-pathogenic bacteria that can balance the gut micro diversity in combating COVID-19 [27]. These are some indirect evidence found in the case of COVID19; still, there is a need to understand more about the SARS-CoV-2 and its effect on gut microbiota [27]. It is likely to be good potential for effective vaccine design for COVID19.
Bioinformatics and Vaccine Design
With the advancement of Next-generation sequencing (NGS) technologies, a new dimension to study microbiota is developed [28]. These studies characterize microbial communities, their specific environment, and interaction with humans. Comprehensive methods like 16S rRNA, short- gun metagenomics, and metatranscriptomics are presently available to study microbiota [29].
- 16S rRNA gene sequence analysis provides taxonomic content and community comparison and similarity analysis.
- In short-gun sequencing: Viromescan is an open- source tool, specifically developed to analyze virome taxonomy. This study will enrich viral reads from the metagenomic dataset and map them on a hierarchical viral data. This step informs the new virus detection for functional analysis of gene prediction. The short-gun metagenomics offers extensive knowledge of genomes of all the microbes consisting of the microbiota.
- Metatranscriptomics is the complete survey of the whole transcriptome of a microbial community. It is a good investigation of gene expression and possible function of the human microbiome in a specific tissue or specific organ with a particular condition [30].
These will reveal information about the human microbiome relation as per health and disease conditions. This study with respect to COVID-19 will better give insights for its prevention and cure. Vaccine efficacy and duration of protection could be highly recommended based on these modern technologies. The present scenario of COVID19 has given us a chance to again study microbes’ diversity while vaccine candidate development [27]. Probiotics vaccine adjuvants are in the stage of development. Next generation sequencing, metagenomics and transcriptomics will play significant role in vaccine development of COVID19. As these experimental methods informs the taxonomic diversity and provide the information of microbes as functional profiles with various conditions. These analyses will have the power of showing the host immune response whether cell-mediated or humoral on vaccine. These system biology approaches apply important opportunity to integrate data related to both Microbiome and host response for vaccines. Diet, sex, age will also play a critical role for host- gut microbe interaction with respect to COVID19 [31].
Conclusion
Hence an effective nutritional strategy and particular food habits for each human which can enrich microbiota are the great need of an hour. Covid-19 pandemic teaches us to follow a dietary chart as per the symptoms appear and therapeutics given. Researches need to be conducted to examine the effect of COVID-19 on microbiota profiling especially gut microbes. Not only bacteria, fungi, and phages are also the gut niche. Lung microbiota is really needed to be investigated. These studies may further improve the way of Vaccine design against COVID19 and play a crucial role in taking pivotal measures in the near future. And it is the most exciting area of research this will open new insights for medicines in the modern world. Moreover very soon precision nutrition will be provided to each and every infected person.
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