Culture Vaccine Research Articles

Effect of dry period immunization of Salmonella Dublin latent carriers with a commercial live culture vaccine on intrauterine transmission based on the presence of precolostral antibodies in offspring

Salmonella Dublin latent carrier cows represent a high risk for infection of newborn calves via intrauterine transmission and shedding of bacteria in feces and colostrum at calving. Vaccination of these latent carrier dams during late gestation boosts immunity against S. Dublin. This could reduce the activation of the dormant bacteria during the periparturient immune dysfunction period, thereby reducing the risk of early-life infection in the offspring. Thus, the objective of this study was to evaluate the extent to which vaccinating S. Dublin latent carrier cows at dry-off with a commercial live culture vaccine reduces bacterial shedding at calving and intrauterine infection to calves. To identify latent carriers, we screened 1,084 cows in 4 Michigan commercial dairy farms with a history of S. Dublin. Cows were defined as latent carriers when they showed 3 consecutive positive milk antibody ELISA tests conducted every 2 mo. Subsequently, 148 latent carriers were randomly allocated to the vaccine or control group. Vaccine cows received a commercial live culture vaccine subcutaneously (SC) at dry-off and a booster 2 weeks later. Control cows received saline SC at the same times. At calving, we collected fecal and colostrum samples from the dam and a pre-colostral serum sample from the calf. Bacterial shedding was evaluated in feces and colostrum both qualitatively and quantitatively through bacterial culture and qPCR, respectively. Intrauterine transmission was defined when a calf was positive for serum antibody ELISA at birth. Vaccination decreased the likelihood of calves being born S. Dublin seropositive (Relative Risk [95%CI]) = 0.19 [0.04 - 0.84]). However, no S. Dublin positive isolates were identified through either bacteriological culture or qPCR in feces or colostrum. Vaccination of S. Dublin latent-carrier cows at dry-off reduced intrauterine transmission to calves. Further research is warranted into the potential of vaccination to decrease vertical transmission of S. Dublin in dairy farms. Additionally, the absence of S. Dublin positive fecal and colostrum samples warrants further evaluation of the detection methods for identifying latent carriers or S. Dublin isolation, as well as the role of latent carriers in infecting newborn calves in the maternity area at birth.

Antibody response to sequential vaccination with cell culture, recombinant, or egg-based influenza vaccines among U.S. adults

ABSTRACT The immune response to inactivated influenza vaccines (IIV) is influenced by multiple factors, including hemagglutinin content and egg-based manufacturing. Only two US-licensed vaccines are manufactured without egg passage: cell culture-based inactivated vaccine (ccIIV) and recombinant vaccine (RIV). We conducted a randomized open-label trial in central Wisconsin during the 2018–19 and 2019–20 seasons to compare immunogenicity of sequential vaccination. Participants 18–64 years old were randomized 1:1:1 to receive RIV, ccIIV or IIV in strata defined by number of influenza vaccine doses in the prior 3 years. They were revaccinated with the same product in year two. Paired serum samples were tested by hemagglutination inhibition against egg-adapted and cell-grown vaccine viruses. Serologic endpoints included geometric mean titer (GMT), mean fold rise, and percent seroconversion. There were 373 participants randomized and vaccinated in 2018–19; 332 were revaccinated in 2019–20. In 2018–19, RIV and ccIIV were not more immunogenic than IIV against A/H1N1. The post-vaccination GMT against the cell-grown 3C.2a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .001) and RIV vs ccIIV (p = .001). The antibody response to influenza B viruses was similar across study arms. In 2019–20, GMT against the cell-grown 3C.3a A/H3N2 vaccine virus was higher for RIV vs IIV (p = .03) and for RIV vs ccIIV (p = .001). RIV revaccination generated significantly greater backboosting to the antigenically distinct 3C.2a A/H3N2 virus (2018–19 vaccine strain) compared to ccIIV or IIV. This study adds to the evidence that RIV elicits a superior immunologic response against A/H3N2 viruses compared to other licensed influenza vaccine products.

The cell cultures in virology: from the past to the future

The aim of the review is to give a brief characteristic of cell cultures obtained from mammalian tissues and to consider the current possibilities and prospects for their use in virology.
 The analysis of the literature data presented in the main databases, such as Web of Science, PubMed, Scopus, Elsevier, Google Scholar and RSCI (as of July 2023), indicates that various types of cell cultures are currently used in virological studies. The use of cell culture has a number of advantages over other in vitro and in vivo methods of virological research. The review provides numerous examples on the development of new methods of obtaining cell cultures for the cultivation of viruses. Among them are sensitive and reporter cell systems, the design of which can be a promising tool for diagnostics of existing and new unknown viral infections. Cell cultures are characterized as potential in vitro models in virology for developing new diagnostic test-systems and antiviral drugs. An important area of cell cultures application is their use as a substrate for the production of culture-derived vaccines. Another aspect of the cell cultures application is also highlighted, such as the study of the effect of the viruses on the host immune system or the mechanisms of immunopathogenesis of viral infections. It is concluded that the use of cell cultures remains currently and in the near future one of the most important methods in practical virology and in scientific research.

Awareness on Recent Guidelines for Rabies Prophylaxis among Healthcare Professionals in Rewa District, Madhya Pradesh, India: A Questionnaire-based Cross-sectional Study

Introduction: Rabies is a zoonotic disease that can be fatal and continues to impose a significant financial burden on developing countries. Recently, there have been advancements in the introduction of cell culture vaccines and immunoglobulin, as well as the approval of Intradermal (ID) schedules for vaccine administration. Aim: To assess the knowledge of doctors in Rewa District regarding the National Guidelines for Rabies Prophylaxis in 2019. Materials and Methods: A cross-sectional study was conducted, involving doctors from tertiary healthcare centres, district hospitals, and private practices. Data were collected over a period of one month from 206 doctors using a Google form, which included information about their field of practice and their knowledge of recent guidelines on Rabies prophylaxis. Data analysis was performed using the Chi-square test. Results: Out of the 206 doctors surveyed, 92 (44.7%) were male. A 56.7% of the doctors were aware of the regimen and dosage for ID administration of the Anti Rabies Vaccine, (ARV) and 44.6% were knowledgeable about the modification of PostExposure Prophylaxis (PEP) to Pre-Exposure Prophylaxis (PrEP) in the Essen regimen. Furthermore, 70.9% of the doctors were familiar with the dosage of Human Rabies Immunoglobulin (HRIG), while 42.7% knew how to manage animal bites in immunocompromised patients. Conclusion: The study revealed a lack of sufficient knowledge on various aspects of rabies management among the doctors surveyed. This underscores the need for reorientation programs and Continuing Medical Education (CMEs) training to be provided to doctors to enhance their knowledge of rabies and improve the effective management of animal bites.

Liposomal delivery system/adjuvant for tuberculosis vaccine.

As reported by the World Health Organization, about 10 million individuals were infected with tuberculosis (TB) worldwide. Moreover, approximately 1.5 million people died of TB, of which 214,000 were infected with HIV simultaneously. Due to the high infection rate, the need for effective TB vaccination is highly felt. Until now, various methodologies have been proposed for the development of a protein subunit vaccine for TB. These vaccines have shown higher protection than other vaccines, particularly the Bacillus culture vaccine. The delivery system and safety regulator are common characteristics of effective adjuvants in TB vaccines and the clinical trial stage. The present study investigates the current state of TB adjuvant research focusing on the liposomal adjuvant system. Based on our findings, the liposomal system is a safe and efficient adjuvant from nanosize to microsize for vaccinations against TB, other intracellular infections, and malignancies. Clinical studies can provide valuable feedback for developing novel TB adjuvants, which ultimately enhance the impact of adjuvants on next-generation TB vaccines.

Health professionals KAP study on rabies exposure assessment and NTV administration in Ethiopia

Background: Globally, it’s estimated 60,000 human deaths occur due to rabies with 95% of cases occurring in Africa and Asia. Annually, thousands of people are infected with rabies in Ethiopia and more than 2700 people die. In Ethiopia, the neural-based vaccine has been used since the 1950’s. Due to the old method of production, low immunogenicity and vaccine associated adverse events, WHO discourage the use of this vaccine and recommend replacing it with a safe and effective modern cell culture vaccine. There was no specific guidelines and training for this vaccine and health professional mismanage the nerve tissue vaccine (NTV) with cell culture vaccine resulting in vaccination failure. This study identifies professional knowledge, attitude and practice (KAP), vaccine related adverse events and the burden of rabies cases in humans. Methods: Data were collected from health professionals in selected health facilities using structured questionnaire to identify the level of KAP. Results: The study identified overall gaps in the professionals KAP as below standard which is not more than 25%. The majority of the respondents (97%) reported vaccine associated local adverse events followed by 20% systemic complications during vaccination. Only 2.4% of the respondents reported post-vaccine complications. Rabies cases in humans at those covered health facilities were reported to be 32 during the one-year study period with an average of two cases at each facility. Conclusions: Gaps identified in the professional KAP result indicate the need to provide specific training based on standard guidelines. Generally, the study indicates the need to strengthen rabies prevention and control efforts through inter-sectoral collaboration, and facilitating the establishment of facility-based rabies palliative care centers. In addition, it is recommended to work on technology transfer to replace old method of NTV production with safe and effective modern cell culture based anti-rabies vaccine production for effective rabies PEP.

Outcome prediction of the measles vaccination in healthcare employees

Vaccination is the only guarantee for elimination of measles infection. Healthcare workers have a 13- to 19-fold higher risk for contracting measles than the general population. The number of individuals in the population who did not respond to vaccination is up to 10%, and their accumulation may lead to an outbreak of the infection. The aim of our research was to find potential predictors of arising post-vaccination measles antibodies in the panel of biochemical and immunological serum markers in healthcare workers. The group of healthcare workers (n = 76) aged from 19 to 51 years, with proven absence of pre-existing anti-measles antibodies were twice vaccinated 3 months apart with live measles culture vaccine (SPA “Microgen”, Russia). Measles-specific IgG, total IgG, IgM, IgA, IFNγ, IL-6, CRP, total protein, ALT, AST, total bilirubin, urea, creatinine, protein fractions were determined before vaccination, 1 month after vaccination, 1 month following revaccination, 1 year after revaccination. ROC analysis was used to gain access to the diagnostic performance of quantitative variables in predicting a categorical outcome. Development of a predictive probability model for the binary outcome was carried out using logistic regression. IFNγ, total IgG, IgM, total bilirubin, ALT activity at various post-immunization stages may be considered potential laboratory predictors of measles vaccination failures in healthcare workers. Meanwhile, the contents of pre-vaccination IFNγ, and IgG to measles virus after first vaccination proved to be most informative indexes, which formed the basis for the development of regression models predicting the risk of both primary and secondary vaccination failures. These models allowed to develop algorithm for predicting failures of the measles vaccination in healthcare workers that can be used for detection of persons at risk for non-forming specific humoral immunity. This algorithm is primarily focused on search for the persons who have not responded to measles vaccination, including subjects with probable immunodeficiency conditions. We do not exclude that, on the basis of revealed predictors following measles vaccination, it would be possible to build prognostic models of vaccination efficiency for other vaccinemanaged infections.

Developments in Rabies Vaccines: The Path Traversed from Pasteur to the Modern Era of Immunization.

Rabies is a disease of antiquity and has a history spanning millennia ever since the first interactions between humans and dogs. The alarming fatalities caused by this disease have triggered rabies prevention strategies since the first century BC. There have been numerous attempts over the past 100 years to develop rabies vaccineswith the goal of preventing rabies in both humans and animals. Thepre-Pasteurian vaccinologists, paved the way for the actual history of rabies vaccines with the development of first generation vaccines. Further improvements for less reactive and more immunogenic vaccines have led to the expansion of embryo vaccines, tissue culture vaccines, cell culture vaccines, modified live vaccines, inactivated vaccines, and adjuvanted vaccines. The adventof recombinant technology and reverse genetics have given insight into the rabies viral genome and facilitated genome manipulations, which in turn led to the emergence of next-generation rabies vaccines, such as recombinant vaccines, viral vector vaccines, genetically modified vaccines, and nucleic acid vaccines. These vaccines were very helpful in overcoming the drawbacks of conventional rabies vaccines with increased immunogenicity and clinical efficacies. The path traversed in the development of rabies vaccines from Pasteur to the modern era vaccines, though, faced numerous challenges;these pioneering works have formed the cornerstone for the generation of thecurrent successful vaccines to prevent rabies. In the future, advancements in the scientific technologies and research focus will definitely lay the path for much more sophisticated vaccine candidates for rabies elimination.

Does the rise in cases of Kyasanur forest disease call for the implementation of One Health in India?

The viral hemorrhagic illness known as Kyasanur forest disease (KFD), also referred to as monkey fever, is transmitted by ticks. The etiological agent, which was formerly isolated from monkeys, is Kyasanur forest disease virus (KFDV), an RNA virus belonging to the family Flaviviridae. Since 1957, India has reported 400–500 cases annually, with a case fatality rate of 1–3%. Shiroma, Chikkamagalore, Uttara Kannada, Dakshina Kannada, and Udupi are the five regions in Karnataka, India where KFD is highly prevalent, with around 3263 notified cases reported between 2003 and 2012, of which 823 cases were laboratory confirmed.The symptoms of monkey fever can range from mild sickness to severe neurological sequelae. Currently, prophylaxis involves administration of formalin-inactivated tissue culture vaccine. Despite the continuing vaccination programs in endemic areas for KFD, new cases are being reported. The current availability and effectiveness of the vaccine are not enough to provide protective immunity and thus prevent new outbreaks.Our study examined the known literature, knowledge gaps, and host responses associated with KFD. There is a need for robust vector control, public awareness campaigns, mass vaccination programmes, a full understanding of the eco-epidemiological elements of the disease, and implementation of a One Health program. These could all support prevention and management protocols, and thus help to address the issue.

Preclinical Studies of the Specific Activity of the Live Culture Vaccine VACD6 against Smallpox and other Orthopoxvirus Infections

Relevance. The epidemiological situation in the world is characterized by an increase in the incidence of orthopoxvirus infections in humans and animals. In this regard, it is necessary to develop new safe vaccines against these infections.Aim. Conducting preclinical studies on the specific activity of the live vaccine against smallpox and other orthopoxvirus infections VACΔ6 based on the vaccinia virus (VACV) with six deleted virulence genes are presented.Matherials and methods. The studies were performed in accordance with the requirements of the Guidelines for conducting preclinical studies of drugs (immunobiological preparations), the State Pharmacopoeia XIII and the European Pharmacopoeia 7.0.Results and discussion. The vaccine strain VACΔ6 VACV showed significantly reduced neurovirulence in the model of intracerebral administration to suckling mice, and reduced inflammatorynecrotic activity in the model of intradermal administration to rabbits compared to the classical first­generation smallpox live vaccine approved for use in Russia. Preclinical studies of three series of the finished dosage form of the VAC∆6 vaccine showed its authenticity, thermal stability, non­pyrogenicity and safety. Double intradermal vaccination of rabbits at a dose of 106 PFU/animal, a 100% protective effect was provided against the intranasal infection of rabbits with VACV strain HB­-92 at a dose of 1995 LD50 and a double intradermal vaccination of mice at a dose of 106 PFU/animal, full protection was provided against the intranasal infection of mice with ectromelia virus strain K1 at a dose of 56 LD50.Conclusion. Based on the conducted complex of studies, it can be concluded that the created vaccine of the fourth generation VACΔ6 is safer compared to the live smallpox vaccine of the first generation and is not inferior to it in immunogenic and protective properties.

Antibody responses against heterologous H5N1 strains for an MF59-adjuvanted cell culture–derived H5N1 (aH5n1c) influenza vaccine in adults and older adults

ABSTRACT MF59-adjuvanted H5N1, cell culture-derived inactivated influenza vaccine (aH5N1c, AUDENZ®, Seqirus) is available for persons 6 months of age and older. During a pandemic, lack of preexisting immunity to novel influenza strains increases morbidity and mortality. This study examined the potential for an adjuvanted vaccine to provide cross-protection to novel viruses. Two similarly designed studies involving separate cohorts aged 18–64 and ≥65 y assessed immune responses to five heterologous H5N1 influenza strains elicited by two 7.5 μg doses of aH5N1c given 3 weeks apart. Geometric mean titers (GMT) on Days 1 and 43 and Day 43/Day 1 geometric mean ratios (GMRs) were determined with hemagglutination inhibition (HI) and microneutralization (MN). Rates of seroconversion (SC) and percentages of subjects with HI and MN ≥ 1:40 were determined. Significant increases in GMTs were observed on Day 43 after vaccination for all 5 heterologous strains in all ages tested. SC rates were 28–55% and 17–46% among those aged 18–64 and ≥65 y, respectively. MN ≥ 1:40 was observed in 38–100% of younger and 37–97% of older subjects, and HI ≥ 1:40 was achieved by 28–64% of subjects aged 18–64 y and by 17–57% of subjects aged ≥65 y. A SC rate ≥40% (97.5% CI) was met for two heterologous strains tested in adults aged 18–64 y. In adults aged 18–64 and ≥65 y, two 7.5 μg doses of aH5N1c demonstrated increased immunogenicity from baseline against five heterologous H5N1 strains, illustrating the potential for aH5N1c to provide cross-protection against other H5N1 strains.

Efficacy of cell culture-derived influenza vaccines for children: A systematic review and meta-analysis

Efficacy of cell culture-derived influenza vaccines for children: A systematic review and meta-analysis

Inequitable by Design: The Patent Culture, Law, and Politics Behind COVID-19 Vaccine Global Access

COVID-19 vaccine access has been highly inequitable worldwide, with coverage depending largely on a country’s wealth. By the end of 2021, 64.1% of people living in high-income countries had received at least one dose of the vaccine, compared to only 5.4% of those in low-income countries. Similarly, only high- and upper-middle-income countries had received the most effective vaccines. The uneven distribution of these lifesaving vaccines is made complex due to the convergence of several factors, but it suggests that the extraordinary expanding and ossifying market and political power of a few vaccine manufacturers founded on intellectual property and complementary policies is a decisive factor in shaping our healthcare systems and securing equitable access to vaccines. This Article analyzes the power dynamics of vaccine manufacturing and distribution of U.S. pharmaceutical companies in the context of global COVID-19 vaccination. Drawing on the health-justice and law-and-political-economy scholarship of the last decade, this Article demonstrates how a “patent culture” shaped by intellectual property law fundamentally neglects health-equity principles while politicizing healthcare access. These contemporary frameworks suggest that the global COVID-19 vaccine-access problem is the result of avoidable policy choices made by big manufacturers and affluent governments. Despite a long history of inequities in access to healthcare, policy choices—as predicted by Hart’s inverse equity theory—have favored a purposely inequitable-by-design vaccination program driven by the wealth and power of those allowed to control vaccine production and supply globally. Finally, this Article proposes ways to challenge the normalized and institutionalized patent culture that has commodified access to lifesaving medicines beyond national borders. As it examines national and international legal strategies to address the vaccine-access problem, the Article suggests equity-based principles of public value, transparency, and inclusivity to guide healthcare governance and future reformation of the vaccine-access landscape. An interdisciplinary analysis of the first year of the global vaccine rollout provides an account critical to future policies aiming to address the structural conditions needed to attain equitable health outcomes, even after the pandemic.

Immunogenicity studies of nucleic acid-based antirabies vaccines in BALB/c mice

Improved vaccine efficacy has a major impact on future rabies prevention and control. In this systematic review, a comparative assessment of different nucleic acid-based antirabies vaccination tools developed using different methods, in different countries, was undertaken. The comprehensive search was done in three databases. Articles were carefully selected based on predetermined inclusion/exclusion criteria and eight articles were included in this systematic review. Studies have demonstrated dose-dependent immune response following intramuscular vaccination and improved immune response following intranasal vaccination and gene-gun delivery method. Nucleic acid-based antirabies vaccines have shown higher immune response and protective levels in Bagg's albino (BALB/c) mouse models than cell culture-derived vaccines. It has been demonstrated that the route/method of administration and the vaccine formulation could be improved in various ways to enhance immune response following vaccination. These new vaccine tools and their implementation in pre- and postexposure prophylaxis could be further evaluated and to be adopted by rabies endemic countries.

IMMUNOMORPHOLOGICAL CHANGES IN THE ORGANISM OF ROBBIES AFTER APPLICATION OF BOLSHEVAK VACCINES

The article presents the materials of the effect of polyvalent inactivated culture vaccine against infectious rhi-notracheitis, viral diarrhea, parainfluenza-3, respiratory syncytial, rotavirus and coronavirus infection of cattle "BolsheVak" on immunomorphogenesis in rabbits. It was found that double immunization with an interval of 21 days allows for more active development of cellular and humoral immunity in immunized animals.

Construction and characterization of a contagious ecthyma virus double-gene deletion strain and evaluation of its potential as a live-attenuated vaccine in goat.

Contagious ecthyma is a highly contagious viral disease with zoonotic significance caused by orf virus (ORFV) that affects domestic, ruminants and humans. Live attenuated virus and attenuated tissue culture vaccines are widely used in the fight against ORFV, however, the conventional attenuated vaccine strains have many drawbacks. The aim of this project was to construct a promising contagious ecthyma vaccine strain with safety, high protection efficacy and accessibility by genetic manipulation to against the disease. Using a natural ORFV-GS14 strain as the parental virus, recombinant virus, rGS14-ΔCBP-ΔGIF, with double deletions in the genes encoding the chemokine binding protein (CBP) and granulocyte/macrophage colony-stimulating factor inhibitory factor (GIF) was generated and characterized in vitro and in vivo. Results showed that the growth kinetics curve of rGS14-ΔCBP-ΔGIF and parental virus was consistent, both reaching plateau phase at 48 h post infection, which indicated that the double deletion of cbp and gif genes had little impact on the replication properties of the recombinant virus in primary goat testis (PGT) cell cultures compared with the parental virus. The safety of the double gene-deleted virus was evaluated in lambs. The lambs were monitored for 21 days post infection of the recombinant virus and no ORFV associated symptoms were observed in 21 days post-infection except for slight fever and anorexia in 5 days post-infection, and all lambs inoculated with either recombinant virus or PBS exhibited no clinical signs. To assess the protection efficacy of the rGS14-ΔCBP-ΔGIF, groups of four lambs each were inoculated with rGS14-ΔCBP-ΔGIF, rGS14-ΔCBP, rGS14-ΔGIF or PBS and challenged by a wild type virulent ORFV strain that was isolated from proliferative scabby lesions tissues of infected goat at 21-day post-inoculation. During 14 days post-challenging, lambs inoculated with rGS14-ΔCBP-ΔGIF all remained healthy with unimmunized group all infected, while the single gene-deleted viruses only protected 40% to 50% animals. These results indicated that the double gene-deleted recombinant virus could provide complete protection against virulent ORFV challenging. In conclusion, the double gene-deleted recombinant virus strain, rGS14-ΔCBP-ΔGIF, would be a promising candidate vaccine strains with safety, high protection efficacy and availability.

Development and validation of an in vitro titrimetric method for determination of classical swine fever viruses in PK-15 cells

Classical swine fever (CSF) is a highly contagious notifiable disease of pigs caused by CSF virus of Flaviviridae family. Previously, lapinized vaccines were used for the disease control, which has now been replaced with cell culture vaccines. Determination of virus titre is the key factor for development and quality control testing of classical swine fever (CSF) cell culture vaccines. Since CSFV is a non- cytopathic virus, an accurate method for the titration of this virus in cell culture has not yet been reported. Here we present a full proof method of titration of CSF cell culture viruses employing Fluorescent Antibody Technique (FAT) in 24 well plate cover slip culture of PK-15 cells. CSFV monoclonal antibodies (Mab) used in the test bind to the CSF virus particles in the cell cytoplasm of the infected cells and the immune-fluorescence signal is produced by subsequent binding of FITC conjugate with Mab. In this newly developed method, apple green fluorescence is observed in the cytoplasm of the infected cells as the virus multiplies only in the cytoplasm. The nucleus as well as the uninfected cells cytoplasm is stained red without any traces of green fluorescence. Thus, the test clearly differentiates a CSFV infected cell from the uninfected cells in the vicinity, if any, and also from the uninfected controls. The test can also quantify the accurate titres of CSF live viruses in the cell culture vaccines and hence it has wide application in routine virus titration applied for manufacturing of CSF cell culture vaccines, determination of accurate multiplicity of infection (m.o.i.) during infection and quality control of vaccines by the testing laboratories.

Influenza vaccines: where we are, where we are going.

Influenza vaccines are the most useful strategy for preventing influenza illness, especially in the setting of the COVID-19 pandemic. For the coming year (2021/2022) all vaccines will be quadrivalent and contain two influenza A strains [(H1N1)pdm09-like and (H3N2)-like viruses] and two influenza B strains (Victoria lineage-like and Yamagata lineage-like viruses). However, the currently licensed have suboptimal efficacy due to the emergence of new strains and vaccine production limitations. In this review, we summarize the current recommendations as well as new advancements in influenza vaccinations. Recent advances have been aimed at moving away from egg-based vaccines and toward cell culture and recombinant vaccines. This removes egg adaptations that decrease vaccine efficacy, removes the reliance on egg availability and decreases the time necessary to manufacture vaccines. However, even more radical changes are needed if we are to reach the ultimate goal of a universal vaccine capable of providing long-lasting protection against all or at least most influenza strains. We discuss various strategies, including using more stable influenza antigens such as the hemagglutinin stalk and internal proteins as well as new adjuvants, new vaccine formulations, and DNA/RNA-based vaccines that are currently being developed. The currently available vaccines have suboptimal efficacy and do not provide adequate protection against drifted and shifted strains. Thus, the development of a universal influenza vaccine that induces long-lasing immunity and protects against a broad range of strains is crucial.

Acute motor axonal neuropathy following anti-rabies human diploid cell vaccine: A rare case and review

Rationale: Guillain Barre syndrome (GBS) is an acute neurological illness leading to quadriparesis with respiratory involvement. It can be triggered by infections, vaccinations, surgery, trauma, transplantation and drugs. Anti-rabies cell culture vaccines introduced to overcome the high rate of neurological complications associated with tissue based rabies vaccine, can be very rarely associated with GBS.Patient concerns: A 50-year-old female presented with acute severe upper back pain evolving into pure motor quadriparesis following administration of human diploid cell vaccine for rabies.Diagnosis: Acute motor axonal neuropathy variant of GBS following anti-rabies human diploid cell vaccine.Interventions: Intravenous high dose steroids.Outcomes: Patient recovered completely within 1 month.Lessons: Although anti-rabies cell culture vaccines are highly immunogenic and safe, they are rarely associated with GBS. Clinicians should be aware of this link because prompt diagnosis and treatment can result in complete recovery and avoid complications.

Japanese Encephalitis

Japanese Encephalitis (JE) is an endemic vector-borne (mosquitoes) zoonotic flavivirus disease in Asia with severe neurological manifestations (case fatality rate CFR 20–30%; 30–50% of survivors with serious sequelae). Japanese Encephalitis Virus (JEV) is the leading cause of viral encephalitis in Asia and exposes an estimated 3 billion people to the risk of infection. Other regions of the world have conditions suiting JEV without circulation of the virus (yet). Most JEV infections are asymptomatic or only cause mild symptoms. 1 in 250 infections progresses to severe disease for which no specific treatment is yet available. Neutralizing antibodies develop after infection. In endemic areas this occurs usually during childhood followed by subclinical re-exposure with life-long immunity protecting against disease. Disease in adult populations in endemic areas is rare. General prevention includes avoidance of mosquito bites, e.g., repellents, long-sleeved clothes, coils and vaporizers. Vaccine prevention: Neutralizing antibodies (PRNT50 titer ≥ 1:10) is the correlate of protection. Vaccines currently used are live attenuated JE vaccines and recombinant chimeric JE vaccines (mostly in endemic countries) and cell culture-derived inactivated JE vaccines (travelers, endemic countries). As animal reservoirs of the JEV cannot be eradicated, universal vaccination of humans can control the disease in humans. Optimal JE control in endemic countries is limited by issues around vaccine supply, surveillance (burden of disease underestimation), and resource competition / prioritization.