Tuesday, December 10, 2019

Effects of Influenza vaccine-Samples for Students-Myassignmenthelp

Question: Write a Literaute Review on the Influenza Vaccine. Answer: Introduction The paper deals with the literature review of the Influenza vaccine. In response to viral infection, the vaccination developed against it is discussed. A through literature review is performed to discuss the discovery of vaccine and its format. The paper also highlights the side effects of the vaccination. The impact of the vaccination on various disease rates has been discussed. Further research in this area and improvement in the vaccine formulation has been comprehensively discussed. Influenza- disease details Influenza is an infectious disease also known as flu that effects the respiratory system. Influenza viruses are the RNA virus, of Orthomyxoviridae family, which affects the birds and mammals. This infection is characterised by the symptoms including severe headache, muscle pain, coughing, sore throat, chills, fever and fatigue. It is typically transmitted by direct contact with contaminated surfaces, bird droppings, and nasal secretions and is transmitted by air via virus containing aerosols, sneezes, and coughing. The mode of transmission is not absolutely clear. However, airborne aerosols are mostly responsible for infections in majority of cases. There are three types of Influenza viruses that are known to infect humans. It includes influenza A, B and C. The most common circulating types of influenza viruses are A and B. People with weakened immunity, elderly and young children are prone to this infection. They are thus classified as high risk population. Death due to influenza oc curs in seasonal epidemics and result in 3-5 million cases according to WHO. Each year 250000500000 deaths due to influenza are reported globally (Soema et al., 2015). There are number of tests available to diagnose influenza. It includes serology, vial culture, reverse transcription polymerase chain reaction, rapid antigen testing, rapid molecular assays and immunofluoresence assays. The results of these diagnostic tests should be evaluated in reference to other epidemiological and clinical data accessible by the heath care providers. Even in case of negative results, the infection may still persist. The accurate testing seems to be reverse transcription polymerase chain reaction, for detecting the viral RNA (Vemula et al., 2016). Influenza vaccine Vaccines are the effective way to prevent the seasonal and pandemic flu effects. Public acceptance to the vaccination has been found to be moderate inspite of its efficacy in reducing the mortality and morbidity. Vaccination is important to eliminate the serious consequences of the viral infection including pneumonia, bronchitis, secondary bacterial infections, cardiovascular infections and acute respiratory distress. These complications may lead to death if left untreated and scientific studies have revealed that it remains a global threat to this day (Darvishian et al. 2014). The effectiveness of the viral vaccine depends on the age and health of the patients and varies from season to season. Its efficacy also depends on the match of the antigens on the vaccine strains with that of the circulating strains. However, the exact method to determine the efficacy of vaccine effectiveness is debateable (Simonsen et al. 2007). Public perceives that the illness caused by the Influenza virus is similar to the illness caused by the respiratory pathogens. Since it appears to be similar disease, the public perceive that vaccination would be ineffective consequently reducing its uptake by the patients. It is necessary to know the relative contributions of the influenza and other respiratory infections to influenza like illness. This data must be collected in the context of older community-dwelling adults (Van Beek et al., 2017). The burden of infection and preventing it becomes more challenging with the secondary bacterial infections. The immune response to the vaccination decrease with the age due to immunosenescence (Haq McElhaney, 2014). A lower antibody response in older people (65 years or more) is observed when compared to younger adults. In order to reduce the burden of disease, there is need of developing influenza vaccine that will offer enhanced immunogenicity in older patients. One of the effective means to increase the immunogenicity is to target efficient intradermal vaccination route (Holland et al. 2008). This will ensure best outcomes in the vulnerable population. The format of the vaccine According to Soema et al., (2015) the current influenza vaccine are trivalent formulations, which contain inactivated influenza antigens. These vaccines are derived from two influenza A strains and one influenza B strain. Recently, quadrivalent influenza vaccines have joined this formulations containing an additional strain of influenza B. The first strain is A (H1N1): an A/Michigan/45/2015 (H1N1)pdm09 - like virus. It is the new strain different from that developed in 2016. The other A strain (H3N2) is A/Hong Kong/4801/2014 (H3N2) - like virus. The first B strain is like B/Brisbane/60/2008 virus and the second B strain is like B/Phuket/3073/2013 virus that is added to make the formulation quadrivalent. The four vaccines are as follows- FluarixTetra (GSK)- administered to 3 years old and above FluQuadri(Sanofi Pasteur)- administered to 3 years old and above FluQuadri Junior(Sanofi Pasteur) for children from 6 months-3years of age Afluria Quad(Seqirus)- administered to 18 years and above These triavent and quaadrivalent vaccine injections contains the inactivated form of the virus. The nasal spray formulations contain live attenuated influenza vaccine. It is the attenuated or weak form of virus. The format of the vaccine is to contain error-prone polymerase. It helps to accumulate genetic mutations. These are selected for hemagglutinin (HA) and neuraminidase. The later is the major glycoproteins on the viral surface. This format of vaccine mediates protection in body thorough HA-specific antibodies. T cell responses and antibodies against NA reduces disease severity (Soema et al., 2015). Accordig to Darvishian et al. (2014) the risk of pneumonia, and subsequent death due to hospitalisation were found reduced by many studies. For meta-analysis the author reviewed cohort observational studiesthat conducted mortality assessment. Further, the author also considered 1 randomized, double-blind, placebo-controlled trialand cost-effectiveness studies of the vaccine ranged from 32% to 45% reducing pneumonia and hospitalisation. The efficacy to reduce deaths due to influenza and pneumonia in hospitals ranged from 31% to 65%. The vaccine was found 43% to 50% effective against respiratory condition that caused hospital deaths. In addition this vaccine was also effective in preventing deaths from all causes. The results from the randomise trials showed 50% efficacy of the vaccine in decreasing the in influenza-related illness. The results from the cost effective studies highlighted the influenza vaccine is effective in preventing the mortality and morbidity associated with the di sease. Thus, this vaccine is concluded to be cost savior for each person vaccinated per year. Side effects of vaccine The author of the paper clinical safety data management: definitions and standards for expedited reporting e2a reported adverse effects of the influenza vaccine. The data was recorded according to the ICH experts (International Conference on Harmonisation). The experts reported that influenza vaccine caused adverse events (ICH Harmonised Tripartite Guideline, 2017). The vaccine has side effects that are regarded as solicited systemic reactions. It includes headache, fever, chills, malaise and, myalgia. The injection site reactions solicited are erythema, induration, pain, ecchymosis, swelling, and pruritus. These adverse reactions were recorded for seven days after vaccination. In some cases reactions were recorded after 28 days of vaccination a even serious adverse events were observed by experts after six months of vaccination (DiazGranados et al., 2015). The injection site reactions were further graded as per the size of the are affected. The swelling, erythema, ecchymosis, and induration,were recognized as grade 1 if 5 com. Fever of grade 1 was identified with body temperature of 37.5 ?C to 38 ?C, grade 2 with further rise in tempertaire and 3 with temperature greater than 39?C. If the systemic reaction both solicited and unsolicited were noticeable then it was considered as grade 1, provided they did not interfere with daily activities. Those in grade 2 interfered with activities of daily living and grade 3 adverse events prevented the daily living activities (Pepin et al., 2016). Effect of the vaccine on the disease The effect of the influenza vaccine on the disease was assessed by various randomised control trials. With the vaccine administration the spread of infection was found to decrease. They study by Falsey et al. (2009) conducted a randomised controlled trials to determine the safety of the intradermal (ID) trivalent influenza vaccine of high dose and compare with the standard dose in older adults above 65 years of age. ID vaccines in older adults where more immunogenic, then the SD vaccine. The HA titres were increased for both the A strains by the influenza vaccine and was found slightly less for the B strain. In case of high dose older adult recipients, post-vaccination seroconversion rates, geometric mean titers, and most seroprotection rates were significantly higher when compared to standard dose recipients. Overall, both the ID and the high dose vaccines were more immunogenic and tolerable in older adults. The results with the young adults and older adults gave comparable results (Tsang et al. 2014). Improvement in the vaccine The currently available vaccines have several limitations. In addition, the compressed production times and the complex manufacturing process trigger the need of new type of vaccines. New types of vaccines are required to be formulated, which are more reliable, effective, rapid and involves use advance production technology. In addition, to these properties, the vaccines must be effective and safe to elicit antibodies. It will ensure licensing of the new vaccines. The new vaccines are designed with the aim of increasing the surge capacity in the pandemic situation. Thus, multiple approaches are under way to address these new demands. The efficacy of the new vaccines must be correlated with the immune responses that are les traditional including cellular responses, and antibodies against NA or M2 (Lambert Fauci, 2010). Recombinant proteins These proteins are in last stage of development. These are Cold adapted influenza vaccine This vaccine has protected millions of children in Russia. The licence for making such vaccine in US has not been approved yet. These vaccines allows live virus to be administered through nasal spray (containing isotonic solution of weakened virus particle). It is more effective than the intradermal and intramuscular option. These vaccines were produced with better cross-protective immunity. These vaccines trigger long lasting immunity. They induce local neutralizing immunity and cell mediated immune responses. These vaccines have massively reduced the secondary bacterial infections particularly for children upto 9 years of age (Tlaxca et al., 2015). Genetically engineered live influenza virus vaccines This new vaccine approach uses technique of engineering to introduce sire directed changes in the viral genome (negative-strand RNA) and other unique properties that are then contained by vector (Si et al., 2016). Live influenza virus vaccine candidates expressing altered NS1 genes The influenza virus can be protected from the plasmid (vector) transfected cells. For better stability, the insertions and deletions can be introduced in the genome to alter the NS1 gene to give protection against H5N1 and H9N2 avian influenza virus (Choi et al., 2015). Use of replication-defective influenza viruses as vaccine candidates With the help of the biotechnology tools, it is easy to construct viral particles that undergo single cycle of replications and can be inserted into appropriate vector. These candidates of vaccine hold high potential of inducing long lasting antibody immune response. Cell mediate immune response is stimulated without allowing the infectitious virus to replicate (Lee et al., 2014). Universal vaccines Universal vaccines are enthusiastically developed with increasing optimism due to results from the animal models. The purpose of formulating the universal vaccine is the goal of stimulating the humoral and cellular responses in body similar to the natural infection. The universal vaccines are intended to develop with the ability of long lasting and cross-strain protection. The main target when developing universal vaccine is the conserved epitopes from the influenza NP, HA proteins and matrix 1 (M1), and highly conserved external domain of the influenza matrix 2 (M2) protein. The results from clinical testing showed that the vaccine when administered alone or along with the carrier protein or adjuvant had effective outcomes. In animal models two-step vaccination strategies have been used. The first dose comprise of DNA-based HA vaccine priming and later second dose with an attenuated, inactivated, or adenovirus-vectorbased vaccine. The results showed release of cross-neutralizing ant ibodies. Although it may not be possible to generate the true universal vaccine, efforts are made to consider some of its properties (Lambert Fauci, 2010). DNA-based vaccines DNA vaccines were administered in animal models are. These vaccines are plasmid DNA coated with influenza viral proteins. These vaccines showed promising results in animal models and requires universal approach to make it effective for human use (Stachyra et al., 2014). Viral vectors Viruses that cannot replicate or cause disease are used to deliver the viral protein of influenza. The later are cloned into viruses like vaccinia, adenoviruses, and baculoviruses acting as vector to contain vaccine. Results from trials show promising results in eliciting cellular and antibody response (). Virus like particles Influenza vaccines can be developed from virus like particles that are non-infectious. Cultured cell can be infected with the Recombinant viral vectors. These vectors may express HA, M1 protein of influenza, and NA. These proteins can self assemble at plasma membrane. They can bud from the infect cells as new virus that can enhance immune system (Soema et al., 2015). New adjuvant approaches Current vaccines are administered by intramuscular injections. Liposome like preparations are been recently developed to improve the immunogenicity. The liposome vesicle contains contain cholesterol and viral particles. When delivered subcutaneously or intranasally in mice, showed effective results. However, there is a need of more accurate results to prove its efficacy (Lee et al., 2014). Conclusion In the field of vaccine development a significant improvement have been witnessed. New vaccine technologies hold promising results and are anticipated to give enhanced protection. These vaccines are on the process of development and can be used for human purpose after approval. Efforts are made to reduce the mismatches between the vaccine strains and circulating viruses. In order to make decision there is need of more clinical studies determining the efficacy of the vaccine against placebo and standard vaccines. References Choi, E. H., Song, M. S., Park, S. J., Pascua, P. N. Q., Baek, Y. H., Kwon, H. I., ... Kim, C. J. (2015). Development of a dual-protective live attenuated vaccine against H5N1 and H9N2 avian influenza viruses by modifying the NS1 gene.Archives of virology,160(7), 1729-1740. Darvishian, M., Bijlsma, M. J., Hak, E., van den Heuvel, E. R. (2014). Effectiveness of seasonal influenza vaccine in community-dwelling elderly people: a meta-analysis of test-negative design case-control studies.The Lancet Infectious Diseases,14(12), 1228-1239. 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