Live unattenuated vaccines for controlling viral diseases, including COVID-19.

Live unattenuated vaccines (LUVs) have been neglected for decades, due to widespread prejudice against their safety, even though they have successfully controlled yellow fever and adenovirus infection in humans as well as rinderpest and infectious bursal disease in animals. This review elucidated that LUVs could be highly safe with selective use of neutralizing antivirus antibodies, natural antiglycan antibodies, nonantibody antivirals, and ectopic inoculation. Also, LUVs could be of high efficacy, high development speed, and high production efficiency, with the development of humanized monoclonal antibodies and other modern technologies. They could circumvent antibody-dependent enhancement and maternal-derived antibody interference. With these important advantages, LUVs could be more powerful than other vaccines for controlling some viral diseases, and they warrant urgent investigation with animal experiments and clinical trials for defeating the COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2.

Exploiting vita-PAMPs in vaccines.

Live attenuated vaccines elicit stronger protective immunity than dead vaccines. Distinct PAMPs designated as vita-PAMPs signify microbial viability to innate immune cells. Two vita-PAMPs have been characterized: cyclic-di-adenosine-monophosphate (c-di-AMP) and prokaryotic messenger RNA (mRNA). c-di-AMP produced by live Gram-positive bacteria elicits augmented production of STING-dependent type-I interferon, whereas prokaryotic mRNA from live bacteria is detected by TLR8 enabling discrimination of live from dead bacteria. Bacterial mRNA from live Gram-negative bacteria triggers a heightened type-I interferon and NLRP3 inflammasome response. By mobilizing unique viability-associated innate responses, vita-PAMPs mobilize adaptive immunity that best elicits protection, including follicular T helper cell and antibody responses. Here, we review the molecular mechanisms that confer the unique adjuvanticity of vita-PAMPs and discuss their applications in vaccine design.

Vaccination in Primary Immunodeficiency Disorders.

Immunocompromised patients have increased susceptibility to vaccine-preventable infections. Thus, vaccination is a critical issue in this population. Vaccines are usually classified as live versus inactivated or subunit (nonviable) vaccines. In general, inactivated vaccines are safe in immunocompromised patients and should be given per the routine schedule except when they are unlikely to have any benefit as in severe antibody deficiency or combined immunodeficient patients and patients receiving immunosuppressive therapy or immunoglobulin replacement. However, viable vaccines usually carry the risk of causing disease, especially in severely immunocompromised patients. Therefore, much greater caution must be exercised with the use of viable vaccines and administration is individualized on the basis of the estimated risk of infections if not vaccinated versus the potential adverse effects of the vaccine itself. In this review, we make clear recommendations on the basis of available evidence regarding both routine and specialized vaccines, viable and nonviable, and the degree of immune compromise in all the categories of immunodeficiency disorders.

Immunization with a thermostable newcastle disease virus K148/08 strain originated from wild mallard duck confers protection against lethal viscerotropic velogenic newcastle disease virus infection in chickens.

Newcastle disease (ND) is one of the most devastating poultry infections because of its worldwide distribution and accompanying economical threat. In the present study, we characterized the ND virus (NDV) K148/08 strain from wild mallard duck, with regard to safety, thermostability, immunogenicity, and protective efficacy against velogenic ND viral infection. The NDV K148/08 strain offered enhanced immunogenicity and safety relative to commercially available vaccine strains. The NDV K148/08 strain was safe in 1-day-old SPF chicks after vaccination using a coarse or cabinet-type fine sprayer. We demonstrated that the NDV K148/08 strain elicited high levels of antibody responses and provided protective efficacy against lethal NDV challenge. In addition, the thermostability of the NDV K148/08 strain was as high as that of the thermostable V4 strain. Therefore, the NDV K148/08 strain may be useful to ensure NDV vaccine performance and effectiveness in developing countries, especially in remote areas without cold chains.