Adenovirus vector vaccines

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirus（Ad） vector vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019（COVID-19）, worldwide.Alternate :抄録非増殖型アデノウイルスベクターは、in vivoへの直接投与において優れた遺伝子導入活性を示すことから、病原体由来の抗原タンパク質を発現させることにより、新興・再興感染症に対するワクチンベクターとして積極的な開発が進められてきた。最近では、新型コロナウイルス感染症（COVID-19）に対するワクチンとして、欧米中露において迅速な実用化がなされた。本稿では、アデノウイルスベクターの特性、COVID-19に対するアデノウイルスベクターワクチンの特徴、およびアデノウイルスベクターワクチンの可能性について解説する。

The Pandemic Puzzle-Reviewing the Existing Pieces, Searching for the Missing Ones

The research carried out on socioeconomic implication models of (re)emerging infectious diseases triggering pandemics has shown us that these largely depended on infection transmission, conditioned by the type of pathogen and the human host. Also, these depended on certain external factors, such as the phenomenon of globalization, pollution, fragile health systems, modification of human behaviors, expansion of human habitat near the outbreaks, favorable vectors involved in the transmission and development of new pandemics and last but not least of wars or civil revolts. The present research attempts to provide some responses to the following questions: 1. What have been the most recent and important emerging infectious disease pandemics and what were the risk factors? 2. What was the socioeconomic impact generated by these pandemics and what important lessons did we learn/identify? 3. What measures and/or directions must be implemented/addressed to prevent/possibly stop a future wave of infections or a new pandemic? The answers to these questions are substantiated by different indicators (transmission potential and pathogen severity) through which we focused to offer some suggestions/directions regarding the way in which these pandemics could be anticipated or prevent, indicators that otherwise are already used by public authorities in the development and exploration of intervention strategies. However, through the elaboration and staged presentation of how these pandemics acted as well as the socioeconomic implications and human reactions, this research could be useful in leading to the development of new, effective ways to prevent the transmission of (re)emerging infectious diseases.

New Technological Developments in Identification and Monitoring of New and Emerging Infections

Human population growth, globalization, and climate change may pose a sustained risk of emerging infections of pandemic potential. Fortunately, technological development provides tools to identify and monitor emerging epidemics. The rapid full genome characterization of the SARS coronavirus-2 (SARS-CoV-2), responsible for coronavirus infectious disease 2019 (COVID-19), and free sharing of sequence information, enabled a rapid global response. This included diagnostics, epidemiological monitoring, nonmedical interventions, and vaccine development, limiting the pandemic impact. An early and efficient response to global health threats will continue to rely on the development, refinement, and utilization of novel technologies to detect and monitor emerging infectious diseases. © 2022 Elsevier Inc. All rights reserved.

Adenovirus vector vaccines.

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirusAdvector DDS vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019COVID-19, worldwide.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Adenovirus vector vaccines.

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirus(Ad)vector DDS vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019(COVID-19), worldwide.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Adenovirus vector vaccines.

Recently, importance of vaccines for treatment and prevention of emerging and re-emerging infectious diseases has been re-recognized. A replication-incompetent adenovirus(Ad)vector DDS vaccine expressing virus antigen proteins is one of the most advanced platforms as a novel vaccine because an Ad vector vaccine can be rapidly applicable to pandemic. In this review, we describe the basic properties of an Ad vector for vaccine, in addition to the summary of the development of an Ad vector vaccine for emerging and re-emerging infectious diseases, including Coronavirus disease 2019(COVID-19), worldwide.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Revisiting scrub typhus: A neglected tropical disease.

Scrub typhus is an under diagnosed re-emerging vector borne disease caused by an intracellular gram negative bacteria, Orientia. The disease is commonly prevalent in rural and hilly areas of Tsutsugumashi triangle. The diagnosis of the disease is very challenging due to similarity of its early symptoms with other febrile illnesses, like dengue and COVID 19, as well as non-availability of rapid, reliable and cost-effective methods. Moreover, the diverse clinical presentation in severe cases make it significant health problem. The occupational and behavioral risks responsible for the transmission lead to urgent need of vaccine development against the disease. The complete knowledge about its pathogenesis and the interaction with host's immune cells may help the scientists in developing the appropriate diagnostic methods as well as the vaccines.

The perinatal health challenges of emerging and re-emerging infectious diseases: A narrative review.

The world has seen numerous infectious disease outbreaks in the past decade. In many cases these outbreaks have had considerable perinatal health consequences including increased risk of preterm delivery (e.g., influenza, measles, and COVID-19), and the delivery of low birth weight or small for gestational age babies (e.g., influenza, COVID-19). Furthermore, severe perinatal outcomes including perinatal and infant death are a known consequence of multiple infectious diseases (e.g., Ebola virus disease, Zika virus disease, pertussis, and measles). In addition to vaccination during pregnancy (where possible), pregnant women, are provided some level of protection from the adverse effects of infection through community-level application of evidence-based transmission-control methods. This review demonstrates that it takes almost 2 years for the perinatal impacts of an infectious disease outbreak to be reported. However, many infectious disease outbreaks between 2010 and 2020 have no associated pregnancy data reported in the scientific literature, or pregnancy data is reported in the form of case-studies only. This lack of systematic data collection and reporting has a negative impact on our understanding of these diseases and the implications they may have for pregnant women and their unborn infants. Monitoring perinatal health is an essential aspect of national and global healthcare strategies as perinatal life has a critical impact on early life mortality as well as possible effects on later life health. The unpredictable nature of emerging infections and the potential for adverse perinatal outcomes necessitate that we thoroughly assess pregnancy and perinatal health implications of disease outbreaks and their public health interventions in tandem with outbreak response efforts. Disease surveillance programs should incorporate perinatal health monitoring and health systems around the world should endeavor to continuously collect perinatal health data in order to quickly update pregnancy care protocols as needed.

[130th anniversary of virology].

130 years ago, in 1892, our great compatriot Dmitry Iosifovich Ivanovsky (18641920) discovered a new type of pathogen viruses. Viruses have existed since the birth of life on Earth and for more than three billion years, as the biosphere evolved, they are included in interpopulation interactions with representatives of all kingdoms of life: archaea, bacteria, protozoa, algae, fungi, plants, invertebrates, and vertebrates, including the Homo sapiens (Hominidae, Homininae). Discovery of D.I. Ivanovsky laid the foundation for a new science virology. The rapid development of virology in the 20th century was associated with the fight against emerging and reemerging infections, epidemics (epizootics) and pandemics (panzootics) of which posed a threat to national and global biosecurity (tick-borne and other encephalitis, hemorrhagic fevers, influenza, smallpox, poliomyelitis, HIV, parenteral hepatitis, coronaviral and other infections). Fundamental research on viruses created the basis for the development of effective methods of diagnostics, vaccine prophylaxis, and antiviral drugs. Russian virologists continue to occupy leading positions in some priority areas of modern virology in vaccinology, environmental studies oz zoonotic viruses, studies of viral evolution in various ecosystems, and several other areas. A meaningful combination of theoretical approaches to studying the evolution of viruses with innovative methods for studying their molecular genetic properties and the creation of new generations of vaccines and antiviral drugs on this basis will significantly reduce the consequences of future pandemics or panzootics. The review presents the main stages in the formation and development of virology as a science in Russia with an emphasis on the most significant achievements of soviet and Russian virologists in the fight against viral infectious diseases.

Monkeypox virus: A review.

While monkeypox was previously found in Africa, the bulk of occurrences in the present outbreak are being reported in many countries. It is not yet known how this outbreak began, and as the COVID-19 crisis begins to abate, numerous nations throughout the world are now contending with a novel outbreak. Monkeypox is a transmissible virus between animals and humans, belonging to the Orthopoxvirus genus of the Poxviridae family. In the 1970s, cases of monkeypox began increasing due to the cessation of vaccination against smallpox, which drew international attention. The virus was named monkeypox because it was first observed in macaque monkeys. It is thought to be transmitted by several different rodents and small mammals, though the origin of the virus is not known. Monkeypox, while occasionally transmitted from one human to another, can be disseminated through the inhalation of droplets or through contact with the skin lesions of an infected individual. Unfortunately, there is no definitive cure for monkeypox; however, supportive care can be offered to ameliorate its symptoms. In severe cases, medications like tecovirimat may be administered. However, there are no established guidelines for symptom management in monkeypox cases. In this article we have discussed about different aspects of monkeypox including viral structure, transmission, replication, clinical manifestations, vaccination, treatment and current prevalence in the world to understand it better and give insight to the future studies.

Emerging and Re-Emerging Viral Infections: An Indian Perspective.

Emerging and re-emerging viral infections pose a constant threat, especially in healthcare settings. Viral infections can be thought of as an ecological system, like a forest or a pond, with different species competing for resources. Pandemics tend to occur when there is a disruption to this ecosystem, such as introducing a strain of virus into humans or animals that they have no immunity against. Around 60% of human infectious diseases and 75% of emerging infections are zoonotic, with two-thirds originating in wildlife. There is an ongoing risk of viral diseases as the human population continues to grow and the rate of urbanization increases. The emergence and re-emergence of viral diseases are influenced by a variety of virologic and environmental factors. These factors can be roughly categorized as affecting humans, the environment and/or ecology, and viruses. The spread of zoonotic diseases among humans can be prevented by reducing the transmission risk associated with wildlife and exotic pets through education, legislation, and behavioral change programs that target individuals at risk for exposure.

Biological characteristics, biosafety prevention and control strategies for the 2022 multi-country outbreak of monkeypox.

Monkeypox is a zoonotic disease caused by the monkeypox virus (MPXV), which is a potential biological warfare agent of bioterrorism and poses the greatest threat to the world's public biosafety and health after variola virus (VARV). While the coronavirus disease 2019 (COVID-19) pandemic has not ended yet, monkeypox is spreading menacingly. The first case of monkeypox in a nonendemic country was confirmed on May 6th, 2022, while the first imported case from Asia was found on June 21st. There were more than 16 thousand reported cases as of July 23rd, the day the World Health Organization (WHO) declared the global monkeypox outbreak a public health emergency of international concern (PHEIC) at the same level as smallpox and COVID-19; while there were more than 53 thousand cases as of September 1st. Therefore, we will propose relevant biosafety prevention and control strategies after analyzing the etiology of the 2022 multi-country monkeypox outbreak from the biological feature, transmissibility, epidemic, and variability of MPXV.

A replication-competent smallpox vaccine LC16m8Δ-based COVID-19 vaccine.

Viral vectors are a potent vaccine platform for inducing humoral and T-cell immune responses. Among the various viral vectors, replication-competent ones are less commonly used for coronavirus disease 2019 (COVID-19) vaccine development compared with replication-deficient ones. Here, we show the availability of a smallpox vaccine LC16m8Δ (m8Δ) as a replication-competent viral vector for a COVID-19 vaccine. M8Δ is a genetically stable variant of the licensed and highly effective Japanese smallpox vaccine LC16m8. Here, we generated two m8Δ recombinants: one harbouring a gene cassette encoding the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) glycoprotein, named m8Δ-SARS2(P7.5-S)-HA; and one encoding the S protein with a highly polybasic motif at the S1/S2 cleavage site, named m8Δ-SARS2(P7.5-SHN)-HA. M8Δ-SARS2(P7.5-S)-HA induced S-specific antibodies in mice that persisted for at least six weeks after a homologous boost immunization. All eight analysed serum samples displayed neutralizing activity against an S-pseudotyped virus at a level similar to that of serum samples from patients with COVID-19, and more than half (5/8) also had neutralizing activity against the Delta/B.1.617.2 variant of concern. Importantly, most serum samples also neutralized the infectious SARS-CoV-2 Wuhan and Delta/B.1.617.2 strains. In contrast, immunization with m8Δ-SARS2(P7.5-SHN)-HA elicited significantly lower antibody titres, and the induced antibodies had less neutralizing activity. Regarding T-cell immunity, both m8Δ recombinants elicited S-specific multifunctional CD8+ and CD4+ T-cell responses even after just a primary immunization. Thus, m8Δ provides an alternative method for developing a novel COVID-19 vaccine.

Preliminary investigation and intervention of the suspected plague outbreak in Madunga, Babati District-Tanzania.

BACKGROUND: Rodents are known to be reservoirs of plague bacteria, Yesinia pestis in the sylvatic cycle. A preliminary investigation of the suspected plague outbreak was conducted in Madunga Ward, Babati District Council in Manyara Region December-2019-January 2020 Following reported two cases which were clinically suspected as showing plague disease symptoms. METHOD: The commensal and field rodents were live trapped using Sherman traps in Madunga Ward, where plague suspect cases were reported and, in the Nou-forest reserve areas at Madunga Ward, Babati District Council, to assess plague risk in the area. Fleas were collected inside the houses using light traps and on the rodents 'body after anaesthetizing the captured rodent to determine flea indices which are used to estimate the risk of plague transmission. Lung impression smears were made from sacrificed rodents to examine for possible bipolar stained Yersinia spp bacilli. RESULTS: A total of 86 rodents consisting of ten rodent species were captured and identified from the study sites. Nine forest rodent species were collected. Field/fallow rodent species were dominated by Mastomys natalensis. whereas domestic rodent species captured was Rattus rattus. Overall lung impression smear showed bipolar stain were 14 (16.28%) while House Flea Index (HFI) was 3.1 and Rodent Flea Index (RFI) was 1.8. CONCLUSION: The findings of this study have shown that, the presence of bipolar stained bacilli in lung impression smears of captured species of rodents indicates (not confirmed) possible circulation of Yesrsinia pests in rodents and the high flea indices in the area which included the most common flea species known to be plague vectors in Tanzania could have played transmission role in this suspected outbreak. The study recommends surveillance follow-up in the area and subject collected samples to the standard plague confirmatory diagnosis.

Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2.

New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or via the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.

Transmission dynamics and epidemiological characteristics of SARS-CoV-2 Delta variant infections in Guangdong, China, May to June 2021.

BackgroundThe Delta variant of SARS-CoV-2 had become predominant globally by November 2021.AimWe evaluated transmission dynamics and epidemiological characteristics of the Delta variant in an outbreak in southern China.MethodsData on confirmed COVID-19 cases and their close contacts were retrospectively collected from the outbreak that occurred in Guangdong, China in May and June 2021. Key epidemiological parameters, temporal trend of viral loads and secondary attack rates were estimated. We also evaluated the association of vaccination with viral load and transmission.ResultsWe identified 167 patients infected with the Delta variant in the Guangdong outbreak. Mean estimates of latent and incubation period were 3.9 days and 5.8 days, respectively. Relatively higher viral load was observed in infections with Delta than in infections with wild-type SARS-CoV-2. Secondary attack rate among close contacts of cases with Delta was 1.4%, and 73.1% (95% credible interval (CrI): 32.9-91.4) of the transmissions occurred before onset. Index cases without vaccination (adjusted odds ratio (aOR): 2.84; 95% CI: 1.19-8.45) or with an incomplete vaccination series (aOR: 6.02; 95% CI: 2.45-18.16) were more likely to transmit infection to their contacts than those who had received the complete primary vaccination series.DiscussionPatients infected with the Delta variant had more rapid symptom onset compared with the wild type. The time-varying serial interval should be accounted for in estimation of reproduction numbers. The higher viral load and higher risk of pre-symptomatic transmission indicated the challenges in control of infections with the Delta variant.