The simian adenovirus Y25 was chosen as a strategy to circumvent pre-existing immunity to common human adenovirus serotypes which could impair immune responses induced by adenoviral vectored vaccines. Deletion of the E1 gene renders the ChAdOx1 vector replication incompetent and further genetic engineering of the E3 and E4 genes allows for increased insertional capability and optimizes vaccine manufacturing processes. ChAdOx1 vectored vaccines can be manufactured in E1 complementing cell lines at scale and are thermostable. The first ChAdOx1 vectored vaccines approved for human use, against SARS-CoV-2, received emergency use authorization in the UK on 30th December 2020, and is now approved in more than 180 countries.
From 1955 to 1963, an estimated 10-30% of polio vaccines administered in the US were contaminated with simian virus 40 (SV40). The virus came from monkey kidney cell cultures used to make polio vaccines at that time. Most of the contamination was in the inactivated polio vaccine (IPV), but it was also found in oral polio vaccine (OPV). After the contamination was discovered, the U.S. government established testing requirements to verify that all new lots of polio vaccines were free of SV40.
Simian 2.2 PRO
Mohammad-Taheri Z, Nadji SA, Raisi F, Mohammadi F, Bahadori M, Mark EJ. No association between simian virus 40 and diffuse malignant mesothelioma of the pleura in Iranian patients: a molecular and epidemiologic case-control study of 60 patients. Am J Ind Med. 2013 Oct;56(10):1221-5. icon
Eom M, Abdul-Ghafar J, Park SM, Han JH, Hong SW, Kwon KY, Ko ES, Kim L, Kim WS, Ha SY, Lee KY, Lee CH, Yoon HK, Choi YD, Chung MJ, Jung SH. No detection of simian virus 40 in malignant mesothelioma in Korea. Korean J Pathol. 2013 Apr;47(2):124-9. icon
pDC production in bone marrow was not significantly affected by acute SIV infection in this study, although additional studies in a larger cohort of animals are needed to confirm these findings due to the marked variability in pDC number in aspirates. A similar wide variation in pDC number was noted in bone marrow aspirates analyzed from SIV-naïve pig-tailed macaques [32]. No prior reports to our knowledge have investigated the effects of SIV infection on pDC production from bone marrow. Studies in SIV-infected macaques indicate that virus does not infect CD34+ hematopoietic stem cells in vivo [52], although defects in bone marrow hematopoiesis that significantly impact upon the generation of CD4+ T cells from CD34+ progenitors ex vivo have been demonstrated [53]. Our study evaluated pDC kinetics in bone marrow only up to 12 days post infection and it is possible that hematopoietic suppression may not be occurring at this very early stage. Indeed, bone marrow suppression as measured by a decrease in colony forming units is only evident beginning at 21 days post infection of macaques with a pathogenic simian/human immunodeficiency virus [54].
Vector surveillance is essential in determining the geographical distribution of mosquito vectors and understanding the dynamics of malaria transmission. With the elimination of human malaria cases, knowlesi malaria cases in humans are increasing in Malaysia. This necessitates intensive vector studies using safer trapping methods which are both field efficient and able to attract the local vector populations. Thus, this study evaluated the potential of Mosquito Magnet as a collection tool for Anopheles mosquito vectors of simian malaria along with other known collection methods.
Mosquito Magnet has a promising ability to catch An. introlatus and An. cracens, the important vectors of knowlesi and other simian malarias in Peninsular Malaysia. The ability of Mosquito Magnet to catch some of the Anopheles mosquito species is comparable to HLC and makes it an ethical and safer alternative.
Besides, more information on knowlesi malaria vectors is crucial to better understand the bionomics of the vectors and its role in malaria transmissions. The increased cases of knowlesi malaria in Malaysia [4] certainly demand proper vector surveillance to understand the transmission dynamics of simian Plasmodium to humans from its natural macaque hosts. In addition, reports on natural human infection with Plasmodium cynomolgi [6,7,8,9] and possibly other simian Plasmodium necessitate more intensive vector surveillance in Malaysia and the Southeast Asian region. Vector incrimination by gathering site-specific information on the vectors is an essential step in planning effective control measures [10].
Since the Anopheles vectors of knowlesi malaria are forest-dwelling mosquitoes that belong to the Leucosphyrus group [16], the conventional trapping techniques such as HLC can be challenging. This includes the possibilities of encountering dangerous wild animals when sampling in deep forested area for long hours. Thus, lack of data on the spatiotemporal distribution of mosquito species in certain areas can impede the process of understanding the zoonotic transmission dynamics of simian malaria. Although there are other trapping methods that use physical and chemical attractants for vector surveillance (without using humans as bait), each method has its own limitations. In general, all trapping methods and attractants have variable performances compared to HLC for Anopheles mosquitoes sampling [17]. Considering that the current conventional approaches are challenged by many factors, an alternative trapping method is urgently needed for the surveillance of simian malaria vectors.
Mosquito Magnet may offer a novel solution to some of the issues associated with the conventional trapping methods. Mosquito Magnet was originally designed to catch and kill mosquitoes by dehydrating them in the net by trapping them for many days. However, when the mosquitoes are collected within the same day, live mosquitoes can be obtained, which can be dissected for further entomological investigation. Several studies have evaluated the efficiency of Mosquito Magnet in trapping mosquitoes [18,19,20,21,22]. However, all those studies were conducted in countries outside Southeast Asia where different species of Anopheles mosquitoes were caught. Mosquito Magnet was found to be effective in catching Neo-tropical Anopheles species, i.e. An. nuneztovari and An. darlingi, which significantly correlates with the results of HLC, but is not efficient in collecting An. marajoara [23]. These findings call for further investigations to assess the effectiveness of Mosquito Magnet for surveillance of Anopheles populations in Malaysia. Furthermore, the efficacy of the Mosquito Magnet in trapping Anopheles mosquitoes from the Leucosphyrus group, which are the known vectors for knowlesi and simian malaria, has not been determined while other methods such as CDC light traps [24] and human baited traps [25] have been previously evaluated.
A total of 8 out of 507 Anopheles mosquitoes were positive for malaria parasites, all of which came from the Leucosphyrus group (An. introlatus and An. cracens). All the trapping methods collected Anopheles mosquitoes which were positive for simian malaria parasites except the CDC light trap (Table 3). The simian Plasmodium detected in the mosquitoes were P. inui and P. fieldi. None of the mosquitoes were infected with human Plasmodium malaria parasites.
Few studies had previously evaluated different trapping methods for monitoring malaria vectors. These include the conventional trapping methods such as CDC light traps [24], human-baited double net (HDN) traps [25], BG-malaria traps [38, 39] and monkey-baited traps [40] as well as some of the latest methods, including M-Tego [41], Suna traps [42] and electric nets [43]. All these studies agree that different sampling techniques influence the quantity and diversity of the mosquitoes collected. Thus, with the emergence of knowlesi malaria in many countries in Southeast Asia, there is a need for more robust and effective trapping methods which are able to capture the local Anopheles mosquitoes particularly from the Leucosphyrus group, which are the vectors for knowlesi malaria [16] and other zoonotic simian Plasmodium.
This study to our knowledge represents the first description and comparison of Mosquito Magnet to some of the commonly used mosquito trapping methods to sample Anopheles mosquito for malaria studies in Malaysia. Generally, HLC performed best at catching mosquitoes from both the Anophelinae and Culicinae subfamilies. However, HLC has its limitations. Some of the limitations of using HLC include probable variation in the attractiveness of human hosts to mosquitoes due to different body odor [15] and ethical considerations regarding accidental infection with malaria. Detection of simian Plasmodium in the salivary glands of some mosquitoes collected in this study highlights the inherent risk of exposure to infectious bites during the collection period using HLC. In addition, there is the probability of interpersonal variation of skills among the collectors, which can indirectly lead to biasness in the collection. On the other hand, Mosquito Magnet, which does not use humans as the natural bait, can be an alternative strategy that allows standardized sampling conditions for the surveillance of exophagic simian malaria vectors.
Another alternative method commonly used is the HBT. Previous study in Lao PDR showed that HBT had a similar ability to catch Anopheles mosquitoes as HLC but was significantly more efficient than CDC light traps [25]. This was expected since both HLC and HBT use humans as the bait. However, in our studies, HLC caught significantly more Anopheles mosquitoes than both the CDC light trap and HBT. These variations are probably due to the differences in the species of Anopheles mosquitoes caught in the two studies. Although HBT is an ethically acceptable alternative to HLC as it prevents the collectors from being exposed to mosquitoes and other hematophagous insect bites, it still has an underlying danger of exposing the collectors to dangerous wild animals, a similar risk as with the HLC method. This occurs especially when mosquito collections are carried out in forested areas for long periods of time particularly targeting the vectors of simian malaria. There is also concern that HBT might underestimate the true mosquito abundance as mosquitoes would escape through the gap of the outer net when they cannot feed [46]. However, in our study this probability was reduced by collecting the mosquitoes hourly. Another challenge faced with HBT is the difficulty in finding a suitable place to set up the traps in hilly terrains and deep jungles where there is limited flat ground or cleared space. Areas with dense shrubs and bushes can obstruct the mosquitoes from entering the net through the limited gap in HBTs, which is only few centimeters from the ground. The need for a large clear space to set up the HBT posed another challenge to using this method in forested areas. On the other hand, the Mosquito Magnet requires a very small space to set up, and the usage of portable batteries makes it very easy to station the Mosquito Magnet in any area inside the forest and carry out collections after a certain amount of time. 2ff7e9595c
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