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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 -
Atencion Primaria 2019
Topics: Age Factors; Aged; Aged, 80 and over; Cost-Benefit Analysis; Herpes Zoster; Herpes Zoster Vaccine; Humans; Middle Aged; Neuralgia, Postherpetic; Vaccines, Attenuated; Vaccines, Synthetic
PubMed: 31272850
DOI: 10.1016/j.aprim.2019.05.002 -
Cellular Immunology Oct 2020Mycobacterium bovis BCG, a live attenuated tuberculosis vaccine offers protection against disseminated TB in children. BCG exhibits heterologous protective effects... (Review)
Review
Mycobacterium bovis BCG, a live attenuated tuberculosis vaccine offers protection against disseminated TB in children. BCG exhibits heterologous protective effects against unrelated infections and reduces infant mortality due to non-mycobacterial infections. Recent reports have suggested that BCG vaccination might have protective effects against COVID-19, however it is highly unlikely that BCG vaccine in its current form can offer complete protection against SARS-CoV-2 infection due to the lack of specific immunity. Nonetheless, recombinant BCG strains expressing antigens of SARS-CoV-2 may offer protection against COVID-19 due to the activation of innate as well as specific adaptive immune response. Further proven safety records of BCG in humans, its adjuvant activity and low cost manufacturing makes it a frontrunner in the vaccine development to stop this pandemic. In this review we discuss about the heterologous effects of BCG, induction of trained immunity and its implication in development of a potential vaccine against COVID-19 pandemic.
Topics: BCG Vaccine; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Immunity, Innate; Immunologic Memory; Pandemics; Pneumonia, Viral; SARS-CoV-2; Vaccines, Attenuated
PubMed: 32745670
DOI: 10.1016/j.cellimm.2020.104187 -
PLoS Computational Biology Feb 2021Many viral infections can be prevented by immunizing with live, attenuated vaccines. Early methods of attenuation were hit-and-miss, now much improved by genetic...
Many viral infections can be prevented by immunizing with live, attenuated vaccines. Early methods of attenuation were hit-and-miss, now much improved by genetic engineering. However, even current methods operate on the principle of genetic harm, reducing the virus's ability to grow. Reduced viral growth has the undesired side-effect of reducing the host immune response below that of infection with wild-type. Might some methods of attenuation instead lead to an increased immune response? We use mathematical models of the dynamics of virus with innate and adaptive immunity to explore the tradeoff between attenuation of virus pathology and immunity. We find that modification of some virus immune-evasion pathways can indeed reduce pathology yet enhance immunity. Thus, attenuated vaccines can, in principle, be directed to be safe yet create better immunity than is elicited by the wild-type virus.
Topics: Adaptive Immunity; Animals; Humans; Immune Evasion; Immune System; Immunity, Innate; Mice; Th1 Cells; Th2 Cells; Vaccination; Vaccines, Attenuated; Viral Vaccines; Virus Diseases
PubMed: 33524036
DOI: 10.1371/journal.pcbi.1008602 -
Scandinavian Journal of Immunology Aug 2019Tuberculosis (TB) remains one of a major health problem worldwide. Tuberculosis vaccine research has made an extraordinary progress over the past few years. However,... (Review)
Review
Tuberculosis (TB) remains one of a major health problem worldwide. Tuberculosis vaccine research has made an extraordinary progress over the past few years. However, there is still no replacement for the Bacillus Calmette-Guérin vaccine, the only TB vaccine licensed for human use. Therefore, the discovery and development of new TB vaccines remains a priority. This article discusses current strategies used to diversify TB vaccines and includes discussion of the status of efforts to improve protection against Mycobacterium tuberculosis (M tb) infection or TB disease by developing new and safe TB vaccines. This article also highlights the current research efforts in immune-enhancing approaches to improve vaccination efficacy. The development of more effective TB vaccines might have significant impact on global TB control.
Topics: Humans; Mycobacterium tuberculosis; Tuberculosis Vaccines; Tuberculosis, Pulmonary; Vaccination; Vaccines, Attenuated
PubMed: 31054193
DOI: 10.1111/sji.12774 -
Scandinavian Journal of Immunology Oct 2019Bacillus Calmette-Guérin (BCG) remains the only licensed vaccine against human tuberculosis (TB). BCG is a live-attenuated strain of Mycobacterium bovis, with... (Review)
Review
Bacillus Calmette-Guérin (BCG) remains the only licensed vaccine against human tuberculosis (TB). BCG is a live-attenuated strain of Mycobacterium bovis, with limitations in efficacy against respiratory TB, the most common form of the disease responsible for transmission. However, continues to be used in the immunization programmes of different countries in the absence of another alternative. In order to improve BCG efficacy against pulmonary TB, in the current clinical TB vaccine pipeline, there are live-attenuated TB vaccines to replace BCG. This review discusses the current status of the development of live vaccine candidates designed to replace BCG from the rational strategies and immunological challenges to its clinical trial and identify key areas in the next years considered essential to confer improved safety and efficacy over BCG.
Topics: Animals; Humans; Mycobacterium bovis; Mycobacterium tuberculosis; Tuberculosis Vaccines; Tuberculosis, Pulmonary; Vaccination; Vaccines, Attenuated
PubMed: 31055842
DOI: 10.1111/sji.12772 -
Human Vaccines & Immunotherapeutics Nov 2020Hepatitis A represents one of the major public health problems worldwide including India. Vaccination is the most effective way to prevent hepatitis A infection. Two... (Review)
Review
Hepatitis A represents one of the major public health problems worldwide including India. Vaccination is the most effective way to prevent hepatitis A infection. Two types of hepatitis A vaccines-live attenuated (H2 strain) and inactivated (killed) are available for use in clinical practice in India with former having advantage of a single-dose compared to two-dose killed vaccine. One of the important characteristic of an ideal vaccine includes its ability to provide life-long protection. In this article we reviewed the available long-term (≥10 years follow-up) published data on live attenuated hepatitis A (H2 strain) vaccine. The data from country of origin of the vaccine (China) and India establish the long-term immunogenicity, protection, and tolerability. Based on the results of several clinical trials showing long-term protection, single dose of live attenuated hepatitis vaccine can be widely used to protect high-risk population against hepatitis A virus infection and related complications.
Topics: China; Hepatitis A; Hepatitis A Antibodies; Hepatitis A Vaccines; Humans; India; Vaccines, Attenuated; Vaccines, Inactivated
PubMed: 32243237
DOI: 10.1080/21645515.2020.1741997 -
Microbiology Spectrum Oct 2022The yellow fever (YF) live attenuated vaccine strain 17D (termed 17D) has been widely used for the prevention and control of YF disease. However, 17D retains significant...
The yellow fever (YF) live attenuated vaccine strain 17D (termed 17D) has been widely used for the prevention and control of YF disease. However, 17D retains significant neurovirulence and viscerotropism in mice, which is probably linked to the increased occurrences of serious adverse events following 17D vaccination. Thus, the development of an updated version of the YF vaccine with an improved safety profile is of high priority. Here, we generated a viable bicistronic YF virus (YFV) by incorporating the internal ribosome entry site (IRES) from virus into an infectious clone of YFV 17D. The resulting recombinant virus, 17D-IRES, exhibited similar replication efficiency to its parental virus (17D) in mammalian cell lines, while it was highly restricted in mosquito cells. Serial passage of 17D-IRES in BHK-21 cells showed good genetic stability. More importantly, in comparison with the parental 17D, 17D-IRES displayed significantly decreased mouse neurovirulence and viscerotropism in type I interferon (IFN)-signaling-deficient and immunocompetent mouse models. Interestingly, 17D-IRES showed enhanced sensitivity to type I IFN compared with 17D. Moreover, immunization with 17D-IRES provided solid protection for mice against a lethal challenge with YFV. These preclinical data support further development of 17D-IRES as an updated version for the approved YF vaccine. This IRES-based attenuation strategy could be also applied to the design of live attenuated vaccines against other mosquito-borne flaviviruses. Yellow fever (YF) continually spreads and causes epidemics around the world, posing a great threat to human health. The YF live attenuated vaccine 17D is considered the most efficient vaccine available and helps to successfully control disease epidemics. However, side effects may occur after vaccination, such as viscerotropic disease (YEL-AVD) and neurotropic adverse disease (YEL-AND). Thus, there is an urgent need for a safer YF vaccine. Here, an IRES strategy was employed, and a bicistronic YFV was successfully developed (named 17D-IRES). 17D-IRES showed effective replication and genetic stability and high attenuation . Importantly, 17D-IRES induced humoral and cellular immune responses and conferred full protection against lethal YFV challenge. Our study provides data suggesting that 17D-IRES, with its prominent advantages, could be a vaccine candidate against YF. Moreover, this IRES-based bicistronic technology platform represents a promising strategy for developing other live attenuated vaccines against emerging viruses.
Topics: Mice; Humans; Animals; Yellow Fever; Vaccines, Attenuated; Internal Ribosome Entry Sites; Yellow Fever Vaccine; Yellow fever virus; Antigens, Viral; Interferon Type I; Mammals
PubMed: 35980184
DOI: 10.1128/spectrum.02246-22 -
Viruses May 2020Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However,... (Review)
Review
Live-attenuated vaccines (LAVs) have achieved remarkable successes in controlling virus spread, as well as for other applications such as cancer immunotherapy. However, with rapid increases in international travel, globalization, geographic spread of viral vectors, and widespread use of vaccines, there is an increasing need to consider how pre-exposure to viruses which share similar antigenic regions can impact vaccine efficacy. Pre-existing antibodies, derived from either from maternal-fetal transmission, or by previous infection or vaccination, have been demonstrated to interfere with vaccine immunogenicity of measles, adenovirus, and influenza LAVs. Immune interference of LAVs can be caused by the formation of virus-antibody complexes that neutralize virus infection in antigen-presenting cells, or by the cross-linking of the B-cell receptor with the inhibitory receptor, FcgRIIB. On the other hand, pre-existing antibodies can augment flaviviral LAV efficacy such as that of dengue and yellow fever virus, especially when pre-existing antibodies are present at sub-neutralizing levels. The increased vaccine immunogenicity can be facilitated by antibody-dependent enhancement of virus infection, enhancing virus uptake in antigen-presenting cells, and robust induction of innate immune responses that promote vaccine immunogenicity. This review examines the literature on this topic and examines the circumstances where pre-existing antibodies can inhibit or enhance LAV efficacy. A better knowledge of the underlying mechanisms involved could allow us to better manage immunization in seropositive individuals and even identify possibilities that could allow us to exploit pre-existing antibodies to boost vaccine-induced responses for improved vaccine efficacy.
Topics: Animals; Antibodies, Viral; Humans; Immunogenicity, Vaccine; Vaccines, Attenuated; Viral Vaccines; Virus Diseases; Viruses
PubMed: 32397218
DOI: 10.3390/v12050520 -
Emerging Microbes & Infections Dec 2024Genetic changes have occurred in the genomes of prevalent African swine fever viruses (ASFVs) in the field in China, which may change their antigenic properties and...
Genetic changes have occurred in the genomes of prevalent African swine fever viruses (ASFVs) in the field in China, which may change their antigenic properties and result in immune escape. There is usually poor cross-protection between heterogonous isolates, and, therefore, it is important to test the cross-protection of the live attenuated ASFV vaccines against current prevalent heterogonous isolates. In this study, we evaluated the protective efficacy of the ASFV vaccine candidate HLJ/18-7GD against emerging isolates. HLJ/18-7GD provided protection against a highly virulent variant and a lower lethal isolate, both derived from genotype II Georgia07-like ASFV and isolated in 2020. HLJ/18-7GD vaccination prevented pigs from developing ASF-specific clinical signs and death, decreased viral shedding via the oral and rectal routes, and suppressed viral replication after challenges. However, HLJ/18-7GD vaccination did not provide solid cross-protection against genotype I NH/P68-like ASFV challenge in pigs. HLJ/18-7GD vaccination thus shows great promise as an alternative strategy for preventing and controlling genotype II ASFVs, but vaccines providing cross-protection against different ASFV genotypes may be needed in China.
Topics: Swine; Animals; African Swine Fever; Vaccines, Attenuated; Viral Proteins; African Swine Fever Virus; Genotype; Viral Vaccines
PubMed: 38164797
DOI: 10.1080/22221751.2023.2300464