A HIV-1 DNA prime-recombinant Adenovirus Type 5 (rAd5) boost vaccine failed to protect from HIV-1 acquisition. We studied the nature of the vaccine-induced antibody (Ab) response to HIV-1 envelope (Env). HIV-1-reactive plasma Ab titers were higher to Env gp41 than gp120, and repertoire analysis demonstrated that 93% of HIV-1-reactive Abs from memory B cells was to Env gp41. Vaccine-induced gp41-reactive monoclonal antibodies (mAbs) were non-neutralizing, and frequently polyreactive with host and environmental antigens including intestinal microbiota (IM). Next generation sequencing of an IGHV repertoire prior to vaccination revealed an Env-IM cross-reactive Ab that was clonally-related to a subsequent vaccine-induced gp41-reactive Ab. Thus, HIV-1 Env DNA-rAd5 vaccine induced a dominant IM-polyreactive, non-neutralizing gp41-reactive Ab repertoire response that was associated with no vaccine efficacy.
The recent incursion of Highly Pathogenic Avian Influenza A (H5N1) virus into North America and subsequent dissemination of virus across the continent, has had significant adverse impacts on domestic poultry, and has led to widespread mortality in many wild bird species. Here we report the recent spillover of H5N1 into marine mammals in the northeastern United States, with associated mortality on a regional scale. This spillover is coincident with a second wave of H5N1 in sympatric wild birds also experiencing regional mortality events. Viral sequences derived from both seal and avian hosts reveal distinct viral genetic differences between the two waves of infection. Spillover into seals was closely related to virus from the second wave, and one of eight seal-derived sequences had the mammalian adaptation PB2 E627K.
Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic disease, one of whom was confirmed positive for SARS-CoV-2. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on viral and antibody assays. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein Spike (S) mutations associated with mustelids. While we found evidence that angiotensin-converting enzyme II provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin cleavage efficiency. These data support the idea that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. We propose two mechanistically grounded hypotheses for mustelid host adaptation of SARS-CoV-2, with possible effects that require additional investigation.
USA) was notified of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in 3 Malayan tigers (Panthera tigris jacksoni) at a zoo in the state. Felids, including domestic cats and exotic big cats, have greater susceptibility to SARS-CoV-2 infection than other species (1-4). Infected domestic cats can transmit the virus to other cats via respiratory droplets or direct contact (4-6). However, the risk for cat-to-human transmission remains unclear. We investigated the SARS-CoV-2 outbreak in Tennessee to determine its source and provide recommendations to control the spread of infection. The StudyTiger 1, the index case, began showing clinical signs of coronavirus disease (COVID-19), including lethargy,
Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to SARS-CoV-2 infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic COVID-19. We observed no evidence of SARS-CoV-2 transmission into the household ferret population via RT-PCR and ELISA. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein mutations associated with mustelids. While there is evidence that ACE2 provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin activity. These data suggest that host factors interacting with the novel S1/S2 cleavage site are a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection.
H ighly pathogenic avian influenza (HPAI) viruses are of concern because of their pandemic potential, socioeconomic impact during agricultural outbreaks, and risks to wildlife conservation. Since October 2020, HPAI A(H5N1) virus, belonging to the goose/Guangdong H5 2.3.4.4b clade, has been responsible for >70 million poultry deaths and >100 discrete infections in many wild mesocarnivore species (1). As of January 2023, H5N1 infections in mammals have been primarily attributed to consuming infected prey, without evidence of further transmission among mammals.We report an HPAI A(H5N1) virus outbreak among New England harbor and gray seals that was concurrent with a wave of avian infections in the region, resulting in a seal unusual mortality event (UME); evidence of mammal adaptation existed in a small subset of seals. Harbor (Phoca vitulina) and gray (Halichoerus grypus) seals in the North Atlantic are known to be affected by avian influenza A virus and have experienced previous outbreaks involving seal-to-seal transmission (2-7). Those seal species represent a pathway for adaptation of avian influenza A virus to mammal hosts that is a recurring event in nature and has implications for human health. The StudyThe first detections of HPAI clade 2.3.4.4b viruses in North America were in wild and domestic birds in November 2021 in Canada and late December 2021 in the United . Starting on January 20, 2022, avian oropharyngeal or cloacal samples were collected from wild birds by personnel in 4 wildlife clinics in Massachusetts. Additional opportunistic samples were collected in Maine and Massachusetts in response to suspicious avian deaths in seabird breeding colonies. We screened samples from 1,079
Phocine distemper virus (PDV) is a morbillivirus that circulates within pinnipeds in the North Atlantic. PDV has caused two known unusual mortality events (UMEs) in western Europe (1988, 2002), and two UMEs in the northwest Atlantic (2006, 2018). Infrequent cross-species transmission and waning immunity are believed to contribute to periodic outbreaks with high mortality in western Europe. The viral ecology of PDV in the northwest Atlantic is less well defined and outbreaks have exhibited lower mortality than those in western Europe. This study sought to understand the molecular and ecological processes underlying PDV infection in eastern North America. We provide phylogenetic evidence that PDV was introduced into northwest Atlantic pinnipeds by a single lineage and is now endemic in local populations. Serological and viral screening of pinniped surveillance samples from 2006 onward suggest there is continued circulation of PDV outside of UMEs among multiple species with and without clinical signs. We report six full genome sequences and nine partial sequences derived from harbour and grey seals in the northwest Atlantic from 2011 through 2018, including a possible regional variant. Work presented here provides a framework towards greater understanding of how recovering populations and shifting species may impact disease transmission.
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