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Hand, foot, and mouth disease (HFMD) has recently emerged as a major public health concern across the Asian-Pacific region. Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the primary causative agents of HFMD, but other members of the Enterovirus A species, including Coxsackievirus A6 (CVA6), can cause disease. The lack of small animal models for these viruses have hampered the development of a licensed HFMD vaccine or antivirals. We have previously reported on the development of a mouse model for EV71 and demonstrated the protective efficacy of an inactivated EV71 vaccine candidate. Here, mouse-adapted strains of CVA16 and CVA6 were produced by sequential passage of the viruses through mice deficient in interferon (IFN) α/β (A129) and α/β and γ (AG129) receptors. Adapted viruses were capable of infecting 3 week-old A129 (CVA6) and 12 week-old AG129 (CVA16) mice. Accordingly, these models were used in active and passive immunization studies to test the efficacy of a trivalent vaccine candidate containing inactivated EV71, CVA16, and CVA6. Full protection from lethal challenge against EV71 and CVA16 was observed in trivalent vaccinated groups. In contrast, monovalent vaccinated groups with non-homologous challenges failed to cross protect. Protection from CVA6 challenge was accomplished through a passive transfer study involving serum raised against the trivalent vaccine. These animal models will be useful for future studies on HFMD related pathogenesis and the efficacy of vaccine candidates. [ABSTRACT FROM AUTHOR]

Abstract: Currently available influenza vaccines provide suboptimal protection. In order to improve the quality of protective immune responses elicited following vaccination, we developed an oil-in-water nanoemulsion (NE)-based adjuvant for an intranasally-delivered inactivated influenza vaccine. Using a prime-boost vaccination regimen, we show that intranasal vaccines containing the W805EC NE elicited higher titers of serum hemagglutination inhibiting (HAI) antibody and influenza-specific IgG and IgA titers compared to vaccines that did not contain the NE. Similarly, vaccines containing the W805EC NE resulted in higher influenza-specific IgA levels in the bronchoalveolar lavage (BAL) fluid and nasal wash when compared to vaccines formulated without NE. The higher antibody titers in mice immunized with the NE-containing vaccines correlated with reduced viral loads in the lungs and nasal turbinates following a high dose viral challenge. Mice immunized with vaccines containing the W805EC NE also showed a reduction in body weight loss following challenge compared to mice immunized with equivalent vaccines produced without NE. Taken together, our results show that the W805EC NE substantially improves the magnitude of protective influenza-specific antibody responses and is a promising mucosal adjuvant for influenza vaccines and vaccines against other mucosal pathogens. [Copyright &y& Elsevier]

Zika virus (ZIKV) is a global public health concern due to its ability to cause congenital Zika syndrome and lack of approved vaccine, therapeutic, or other control measures. We discovered eight novel rabbit monoclonal antibodies (MAbs) that bind to distinct ZIKV envelope protein epitopes. The majority of the MAbs were ZIKV specific and targeted the lateral ridge of the envelope (E) protein domain III, while the MAb with the highest neutralizing activity recognized a putative quaternary epitope spanning E protein domains I and III. One of the non-neutralizing MAbs specifically recognized ZIKV precursor membrane protein (prM). Somatic hypermutation of immunoglobulin variable regions increases antibody affinity maturation and triggers antibody class switching. Negative correlations were observed between the somatic hypermutation rate of the immunoglobulin heavy-chain variable region and antibody binding parameters such as equilibrium dissociation constant, dissociation constant, and half-maximal effective concentration value of MAb binding to ZIKV virus-like particles. Complementarity-determining regions recognize the antigen epitopes and are scaffolded by canonical framework regions. Reversion of framework region amino acids to the rabbit germ line sequence decreased anti-ZIKV MAb binding activity of some MAbs. Thus, antibody affinity maturation, including somatic hypermutation and framework region mutations, contributed to the binding and function of these anti-ZIKV MAbs. IMPORTANCE ZIKV is a global health concern against which no vaccine or therapeutics are available. We characterized eight novel rabbit monoclonal antibodies recognizing ZIKV envelope and prM proteins and studied the relationship between somatic hypermutation of complementarity-determining regions, framework regions, mutations, antibody specificity, binding, and neutralizing activity. The results contribute to understanding structural features and somatic mutation pathways by which potent Zika virus-neutralizing antibodies can evolve, including the role of antibody framework regions. [ABSTRACT FROM AUTHOR]

Background: Enterovirus 71 (EV71) is a major cause of outbreaks of hand, foot and mouth disease, most frequently in children, and is a public health concern in the Asia-Pacific region. Takeda is developing TAK-021, an inactivated EV71 vaccine candidate based on sub-genogroup B2 strain MS87. In a phase I clinical trial, TAK-021 was safe, well tolerated, and immunogenic in healthy adults and elicited cross-neutralizing antibodies against heterologous EV71 sub-genogroup viruses. TAK-021 confers protection from lethal challenge with a mouse-adapted homologous strain in AG129 mice. However, it has not been determined whether TAK-021 can provide cross-protection against heterologous EV71 sub-genogroups., Methods: We examined the efficacy of TAK-021 against challenge with EV71 sub-genogroups B4, B5, C1, C2, and C4 on day 42 (short-term) and sub-genogroups B5 and C4 on day 120 (long-term) after immunization of human scavenger receptor B2 transgenic (hSCARB2-tg) mice with TAK-021 on days 0 and 28. Antibody titers were monitored over 120 days using plaque reduction neutralization test of the homologous vaccine virus., Results: TAK-021 elicited neutralizing antibody (nAb) in greater than 90% of the mice and nAb persisted through day 120. Challenge of control animals led to weight loss and death, as well as virus detection in various organs and histopathological lesions in the brain. All mice that received two doses of TAK-021 developed nAb and survived a short-term challenge given on day 42, while more than 80% survived a long-term challenge given on day 120. EV71 was detected less frequently and at lower levels in organs of immunized mice compared to non-immunized control mice., Conclusions: The results show that TAK-021 can confer protection in mice against the EV71 sub-genogroups tested., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [LK, and SF are employees of Takeda Vaccines, Inc. SD and FV were employees of Takeda Vaccines, Inc at the time this work was conducted. HD was an employee of Takeda Vaccines, Inc at the time this work was conducted and is a paid consultant to Takeda Vaccines, Inc. KT, MK, AT, KK and SK are affiliated with Tokyo Metropolitan Institute of Medical Science, which received funding from Takeda Vaccines, Inc to conduct this study.]., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bangladesh is one of the vulnerable countries of the world for natural disasters. Drought is one of the common and severe calamities in Bangladesh that causes immense suffering to people in various ways. The present research has been carried out to examine the frequency of meteorological droughts in Bangladesh using the long-term rainfall data of 30 meteorological observatories covering the period of 1948-2011. The study uses the highly effective Standardized Precipitation Index (SPI) for drought assessment in Bangladesh. By assessing the meteorological droughts and the history of meteorological droughts of Bangladesh, the spatial distributions of meteorological drought indices were also analysed. The spatial and temporal changes in meteorological drought and changes in different years based on different SPI month intervals were analysed. The results indicate that droughts were a normal and recurrent feature and it occurred more or less all over the country in virtually all climatic regions of the country. As meteorological drought depends on only rainfall received in an area, anomaly of rainfall is the main cause of drought. Bangladesh experienced drought in the years 1950, 1951, 1953, 1954, 1957, 1958, 1960, 1961, 1962, 1963, 1965, 1966, 1967 and 1971 before independence and after independence Bangladesh has experienced droughts in the years 1972, 1973, 1975, 1979, 1980, 1983, 1985, 1992, 1994, 1995, 2002, 2004, 2006, 2009 and 2011 during the period 1948-2011. The study indicated that Rajshahi and its surroundings, in the northern regions and Jessore and its surroundings areas, the island Bhola and surrounding regions, in the south-west region, were vulnerable. In the Sylhet division, except Srimongal, the areas were not vulnerable but the eastern southern sides of the districts Chittagong, Rangamati, Khagrachhari, Bandarban and Teknaf were vulnerable. In the central regions, the districts of Mymensingh and Faridpur were more vulnerable than other districts., Competing Interests: The authors declare that they have no financial or personal relationships, which may have inappropriately influenced them in writing this article.