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Hong Kong Medical Journal = Xianggang... Dec 2019
Topics: Adolescent; Age Factors; Child; Child, Preschool; Hong Kong; Humans; Immunization Programs; Influenza Vaccines; Influenza, Human; Pandemics; Strategic Stockpile; Time Factors; Vaccines, Attenuated; Young Adult
PubMed: 31889031
DOI: No ID Found -
Genetically modified live attenuated vaccine: A potential strategy to combat visceral leishmaniasis.Parasite Immunology Sep 2020Visceral leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani mainly influencing the population of tropical and subtropical regions across the globe.... (Review)
Review
Visceral leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani mainly influencing the population of tropical and subtropical regions across the globe. The arsenal of drugs available is limited, and prolonged use of such drugs makes parasite to become resistant. Therefore, it is very imperative to develop a safe, cost-effective and inexpensive vaccine against VL. Although in recent years, many strategies have been pursued by researchers, so far only some of the vaccine candidates reached for clinical trial and more than half of them are still in pipeline. There is now a broad consent among Leishmania researchers that the perseverance of parasite is very essential for eliciting a protective immune response and may perhaps be attained by live attenuated parasite vaccination. For making a live attenuated parasite, it is very essential to ensure that the parasite is deficient of virulence and should further study genetically modified parasites to perceive the mechanism of pathogenesis. So it is believed that in the near future, a complete understanding of the Leishmania genome will explore clear strategies to discover a novel vaccine. This review describes the need for a genetically modified live attenuated vaccine against VL, and obstacles associated with its development.
Topics: Animals; Humans; Leishmania donovani; Leishmaniasis Vaccines; Leishmaniasis, Visceral; Vaccines, Attenuated
PubMed: 32418227
DOI: 10.1111/pim.12732 -
Frontiers in Immunology 2022Previous attempts to develop a vaccine against bovine leukemia virus (BLV) have not been successful because of inadequate or short-lived stimulation of all immunity...
Previous attempts to develop a vaccine against bovine leukemia virus (BLV) have not been successful because of inadequate or short-lived stimulation of all immunity components. In this study, we designed an approach based on an attenuated BLV provirus by deleting genes dispensable for infectivity but required for efficient replication. The ability of the vaccine to protect from natural BLV infection was investigated in the context of dairy productive conditions in an endemic region. The attenuated vaccine was tested in a farm in which the prevalence rose from 16.7% in young cattle at the beginning of the study to more than 90% in adult individuals. Sterilizing immunity was obtained in 28 out of 29 vaccinated heifers over a period of 48 months, demonstrating the effectiveness of the vaccine. As indicated by the antiviral antibody titers, the humoral response was slightly reduced compared to wild-type infection. After initial post-vaccination bursts, the proviral loads of the attenuated vaccine remained most frequently undetectable. During the first dairy cycle, proviral DNA was not detected by nested-PCR in milk samples from vaccinated cows. During the second dairy cycle, provirus was sporadically detected in milk of two vaccinated cows. Forty-two calves born from vaccinated cows were negative for proviral DNA but had antiviral antibodies in their peripheral blood. The attenuated strain was not transmitted to sentinels, further supporting the safety of the vaccine. Altogether, these data thus demonstrate that the vaccine against BLV is safe and effective in herd conditions characterized by a very high incidence. This cost-effective approach will thus decrease the prevalence of BLV without modification of production practices. After facing a series of challenges pertaining to effectiveness and biosafety, the vaccine is now available for further large-scale delivery. The different challenges and hurdles that were bypassed may be informative for the development of a vaccine against HTLV-1.
Topics: Animals; Antiviral Agents; Cattle; Enzootic Bovine Leukosis; Female; Leukemia Virus, Bovine; Proviruses; Vaccines, Attenuated
PubMed: 36032174
DOI: 10.3389/fimmu.2022.980514 -
International Journal of Molecular... Jun 2022Influenza is still a frequent seasonal infection of the upper respiratory tract, which may have deadly consequences, especially for the elderly. This is in spite of the... (Review)
Review
Influenza is still a frequent seasonal infection of the upper respiratory tract, which may have deadly consequences, especially for the elderly. This is in spite of the availability of vaccines suggested for persons above 65 years of age. Two types of conventional influenza vaccines are currently licensed for use-live attenuated and inactivated vaccines. Depending on local regulatory requirements, live attenuated vaccines are produced by the reverse genetics technique or by classical reassortment in embryonated chicken eggs. Sometimes, the efficiency of classical reassortment is complicated by certain properties of the wild-type parent virus. Cases of low efficacy of vaccines have been noted, which, among other reasons, may be associated with suboptimal properties of the wild-type parent virus that are not considered when recommendations for influenza vaccine composition are made. Unfortunately, knowledge surrounding the roles of properties of the circulating influenza virus and its impact on the efficacy of the reassortment process, vaccination efficiency, the infectivity of the vaccine candidates, etc., is now scattered in different publications. This review summarizes the main features of the influenza virus that may dramatically affect different aspects of the preparation of egg-derived live attenuated vaccine candidates and their effectiveness. The author expresses her personal view, which may not coincide with the opinion of other experts in the field of influenza vaccines.
Topics: Aged; Female; Humans; Influenza Vaccines; Influenza, Human; Vaccination; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 35743258
DOI: 10.3390/ijms23126815 -
Vaccine May 2021Pertussis, mainly caused by Bordetella pertussis, is a severe respiratory disease that can be fatal, especially in young infants. Vaccines, massively implemented since...
Pertussis, mainly caused by Bordetella pertussis, is a severe respiratory disease that can be fatal, especially in young infants. Vaccines, massively implemented since the middle of the last century, have substantially reduced the pertussis incidence, but have not been able to fully control the disease. One of the shortcomings of current pertussis vaccines is their inability to prevent infection by and transmission of B. pertussis, in contrast to immunity following natural infection. We have developed the live attenuated nasal vaccine BPZE1 and have shown that it prevents both disease and B. pertussis infection in preclinical models. This vaccine is now in clinical development. However, the initial clinical studies have suggested that vaccine take is hampered by pre-existing antibodies to pertactin. Here, we have constructed a pertactin-deficient BPZE1 derivative called BPZE1P in order to overcome this limitation. BPZE1P colonized the murine respiratory tract as efficiently as BPZE1 and induced antibodies at levels similar to those elicited by BPZE1. In the presence of pre-existing antibodies induced by acellular pertussis vaccination, BPZE1P colonized the mouse respiratory tract more efficiently than BPZE1. Both vaccines protected equally well the murine lungs and noses from challenge with laboratory and clinical strains of B. pertussis, including pertactin-deficient strains, against which current acellular pertussis vaccines are less efficient. BPZE1P may thus be an interesting alternative to BPZE1 to overcome vaccine take limitations due to pre-existing antibodies to pertactin.
Topics: Animals; Bacterial Outer Membrane Proteins; Bordetella pertussis; Mice; Pertussis Vaccine; Vaccines, Attenuated; Virulence Factors, Bordetella; Whooping Cough
PubMed: 33896662
DOI: 10.1016/j.vaccine.2021.04.014 -
BMC Microbiology Mar 2021Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases,...
BACKGROUND
Anthrax and smallpox are high-risk infectious diseases, and considered as potential agents for bioterrorism. To develop an effective countermeasure for these diseases, we constructed a bivalent vaccine against both anthrax and smallpox by integrating a gene encoding protective antigen (PA) of Bacillus anthracis to the genome of the attenuated vaccinia virus strain, KVAC103.
RESULTS
Immunization with this bivalent vaccine induced antibodies against both PA and vaccinia virus in a mouse model. We also observed that the efficacy of this vaccine can be enhanced by combined immunization with immunoadjuvant-expressing KVAC103. Mouse groups co-immunized with PA-expressing KVAC103 and either interleukin-15 (IL-15) or cholera toxin subunit A (CTA1)-expressing KVAC103 showed increased anti-PA IgG titer and survival rate against B. anthracis spore challenge compared to the group immunized with PA-expressing KVAC103 alone.
CONCLUSIONS
We demonstrated that the attenuated smallpox vaccine KVAC103 is an available platform for a multivalent vaccine and co-immunization of immunoadjuvants can improve vaccine performance.
Topics: Adjuvants, Immunologic; Animals; Anthrax; Antibodies, Bacterial; Antibodies, Viral; Bacillus anthracis; Mice; Smallpox; Vaccines, Attenuated; Vaccines, Combined; Vaccines, Synthetic; Vaccinia virus
PubMed: 33685392
DOI: 10.1186/s12866-021-02121-5 -
Viruses Aug 2021Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and... (Review)
Review
Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed "latency", which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines' "rational" design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.
Topics: Animals; Drug Design; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Humans; Vaccines, Attenuated; Viral Vaccines
PubMed: 34452501
DOI: 10.3390/v13081637 -
Human Vaccines & Immunotherapeutics Dec 2024Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly... (Review)
Review
Few papers focus their attention on VZV vaccination effectiveness among people living with HIV (PLWH). Flanking the live attenuated vaccine (VZL) available, a newly recombinant vaccine (RZV) was recently introduced and approved for HZ prevention among adults. PLWH represents a population on which a particular attention should be applied, in order to guarantee the vaccine efficacy and safety. We performed a literature search in USNLM, PubMed, PubMed Central, PMC and Cochrane Library. From all the publications found eligible, data were extracted and processed per population, vaccine type, immunogenicity and ADRs. The review of the 13 included studies shows that both RZV and VZL are immunogenic and have an acceptable safety profile in adults and children living with HIV. However, given the lack of research available about vaccine efficacy in preventing VZV and HZ in PLWH, additional studies need to be performed, in order to achieve a full completeness of data.
Topics: Humans; Vaccines, Attenuated; HIV Infections; Herpes Zoster Vaccine; Vaccines, Synthetic; Herpes Zoster; Vaccines, Inactivated; Immunogenicity, Vaccine; Vaccine Efficacy; Herpesvirus 3, Human; Adult; Child; Vaccination; Chickenpox Vaccine
PubMed: 38650460
DOI: 10.1080/21645515.2024.2341456 -
Frontiers in Cellular and Infection... 2022Influenza A viruses (IAV) spread rapidly and can infect a broad range of avian or mammalian species, having a tremendous impact in human and animal health and the global... (Review)
Review
Influenza A viruses (IAV) spread rapidly and can infect a broad range of avian or mammalian species, having a tremendous impact in human and animal health and the global economy. IAV have evolved to develop efficient mechanisms to counteract innate immune responses, the first host mechanism that restricts IAV infection and replication. One key player in this fight against host-induced innate immune responses is the IAV non-structural 1 (NS1) protein that modulates antiviral responses and virus pathogenicity during infection. In the last decades, the implementation of reverse genetics approaches has allowed to modify the viral genome to design recombinant IAV, providing researchers a powerful platform to develop effective vaccine strategies. Among them, different levels of truncation or deletion of the NS1 protein of multiple IAV strains has resulted in attenuated viruses able to induce robust innate and adaptive immune responses, and high levels of protection against wild-type (WT) forms of IAV in multiple animal species and humans. Moreover, this strategy allows the development of novel assays to distinguish between vaccinated and/or infected animals, also known as Differentiating Infected from Vaccinated Animals (DIVA) strategy. In this review, we briefly discuss the potential of NS1 deficient or truncated IAV as safe, immunogenic and protective live-attenuated influenza vaccines (LAIV) to prevent disease caused by this important animal and human pathogen.
Topics: Animals; Humans; Influenza A virus; Influenza, Human; Mammals; Vaccines, Attenuated; Viral Nonstructural Proteins; Virus Replication
PubMed: 35937688
DOI: 10.3389/fcimb.2022.954811 -
Salud Publica de Mexico 2020With the introduction of rotavirus vaccines Rotarix (RV1) or RotaTeq (RV5) in the immunization programs of an increasing number of countries, there is concern that the... (Review)
Review
With the introduction of rotavirus vaccines Rotarix (RV1) or RotaTeq (RV5) in the immunization programs of an increasing number of countries, there is concern that the immune selection pressure induced will cause an increase in the prevalence of virus genotypes not included in the vaccine formulation, or to the appearance of novel rotavirus strains that could evade the protective immune response. The natural fluctuation of rotaviruses makes it difficult to distinguish if the change in the circulating strains is due to the vaccine selective pressure or to the natural diversity fluctuation of viruses. If there has been a selective pressure, it has been low so far. However, it is important to keep an epidemiological surveillance and pay attention to the emergence of strains that are resistant to the vaccine, in particular in those countries where the viral diversity has been shown to be higher.
Topics: Animals; Diarrhea; Genome, Viral; Genotype; Humans; Immune Evasion; Mutation; Rotavirus; Rotavirus Vaccines; Species Specificity; Vaccines, Attenuated; Zoonoses
PubMed: 31869559
DOI: 10.21149/9965