Biology subjects

van Doremalen, N.

Publications and source records attributed to van Doremalen, N..

At least 19 recordsLinked to original sources

bioRxiv2025

Increased contact transmission of contemporary Human H5N1 compared to Bovine and Mountain Lion H5N1 in a hamster model

The ongoing outbreak of highly pathogenic avian influenza virus (HPAIV) subtype H5N1 in the U.S. poses a significant public health threat. To date, 70 human cases have been confirmed in the United States, including two severe cases and one fatality. While suitable animal models are crucial for predicting the potential pandemic risk of newly emerging pathogens in humans, studies investigating contemporary HPAIV H5N1 transmission dynamics remain limited. Here, we investigated the pathogenicity and transmission efficiency of three recent clade 2.3.4.4b H5N1 viruses isolated from a bovine, mountain lion, and a human case using Syrian hamsters. Intranasal inoculation with 104 TCID50 resulted in productive virus replication in the respiratory tract and shedding for all three isolates. Transmission studies showed limited efficiency via direct contact and airborne routes for all three isolates. Although overall transmission was inefficient, the human H5N1 isolate demonstrated relatively greater contact transmissibility than the bovine and mountain lion isolates. Taken together, our data demonstrate that the Syrian hamster model complements existing animal models for influenza A virus research and expands the resources available for investigating the pathogenicity, transmissibility, and efficacy of countermeasures against HPAIV H5N1. One sentence summaryHuman HPAIV H5N1 exhibits comparatively higher contact transmissibility than bovine and mountain lion isolates, despite limited overall transmission.

microbiology↗

bioRxiv2025

Sex bias determines MERS-CoV infection outcomes in a mouse model of differential pathogenicity

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a spectrum of disease outcomes in infected humans, ranging from asymptomatic or tolerant to lethal. While the virus itself contributes to pathogenesis, disease severity is primarily influenced by the hosts response to infection. One factor observed to impact the host response is sex, as epidemiological data indicates that male persons have a higher case fatality rate than females infected with MERS-CoV. However, the mechanism underlying this sex bias is unknown and disease course remains difficult to predict. This study investigates how male and female transgenic mice expressing humanized dipeptidyl peptidase-4 (hDPP4) respond to MERS-CoV infection following exposure to either a tolerance-inducing low dose or lethal high dose. We observed that female hDPP4 mice display dose-dependent tolerance to infection and males experienced uniformly lethal disease in both dosing groups. Longitudinal transcriptomic analysis revealed that males suppress innate and inflammatory responses early after infection, causing delayed induction of the host antiviral response. In contrast, high dose females mount an immediate and sustained interferon and inflammatory response, activating antiviral effectors and interferon-stimulated genes. Tolerant females displayed the greatest transcriptional control, showing no pathway enrichment and minimal changes in weight throughout infection. Our results suggest that the magnitude of the response is driven by dose while the nature of the response in shaped by sex. Females mount a more robust response to MERS-CoV infection, allowing females to tolerate low-dose infection but causing uncontrolled inflammation after high dose infection. In contrast, males experienced lethal outcomes regardless of dose. By examining the dynamics of sex-biased host transcriptional responses in determining disease severity, this study highlights the importance of sex as a biological variable in coronavirus pathogenesis research.

microbiology↗

bioRxiv2024

Enhanced encephalitic tropism of bovine H5N1 compared to the Vietnam H5N1 isolate in mice

In recent years, the landscape of highly pathogenic avian influenza (HPAI) virus infections has shifted, as evidenced by an increase in infections among mammals. This includes the recent circulation of H5N1 in dairy cattle herds in the USA and a rise in associated human cases. In this study, we investigated differences in tissue tropism of two HPAI H5N1 strains, the isolate A/Vietnam/1203/2004 (VN1203) isolated from a fatal human case in 2004 and the bovine isolate A/Bovine/Ohio/B24osu-342/2024 (Bov342) isolated in 2024, in C57BL/6J mice. Infection with either HPAI H5N1 isolate was uniformly lethal in mice. However, tissue tropism differed significantly: while VN1203 replication was largely restricted to the respiratory tract, Bov342 successfully replicated in the respiratory tract as well as various regions of the brain. Bov342-challenged animals exhibited clinical signs consistent with central nervous system (CNS) infection, and infectious virus was detected in brain tissue. Correspondingly, cytokine profiles in the brain differed significantly between the isolates. Notably, in addition to abundant evidence of CNS infection in Bov342-challenged mice via immunohistochemistry, sporadic intranuclear and intracytoplasmic immunoreactivity was observed in other tissues in the head, including the choroid plexus, retina, and inner ear. This study demonstrates that while both HPAI H5N1 isolates are uniformly lethal in C57BL/6J mice upon aerosol exposure, significant differences exist in tissue tropism, with Bov342 resulting in respiratory disease as well as increased neurotropism and inflammation in the brain and nasal turbinates compared to VN1203, which predominantly induces respiratory disease. Significance statementThe rise in HPAI H5N1 infections among mammals, including humans in the USA, highlights an emerging One Health concern. Understanding the phenotypic changes of HPAI H5N1 and associated increase in infection of mammalian hosts is critical. In this study, we investigated the tissue tropism in mice of a bovine HPAI H5N1 strain isolated in 2024 and compared it to a strain isolated from a human patient in 2004. Our findings reveal that the bovine isolate exhibits enhanced neurotropism, unlike the respiratory-restricted replication observed with the HPAI H5N1 isolate from 2004. This difference in tissue tropism, accompanied by distinct cytokine responses in the brain, underscores the potential for altered disease outcomes in other mammalian hosts.

microbiology↗

bioRxiv2024

Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology

The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluated the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compared in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assessed differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicated efficiently in the URT but displayed limited pathology in the lungs compared to previous variants and failed to replicate in human lung organoids. JN.1 was attenuated in both URT and LRT compared to other Omicron variants and failed to transmit in the hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.

microbiology↗

bioRxiv2023

Transmission dynamics of MERS-CoV in a transgenic human DPP4 mouse model

Since 2002, three novel coronavirus outbreaks have occurred: severe acute respiratory syndrome coronavirus (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-2. A better understanding of the transmission potential of coronaviruses will result in adequate infection control precautions and an early halt of transmission within the human population. Experiments on the stability of coronaviruses in the environment, as well as transmission models, are thus pertinent. Here, we show that transgenic mice expressing human DPP4 can be infected with MERS-CoV via the aerosol route. Exposure to 5x106 TCID50 and 5x104 TCID50 MERS-CoV per cage via fomites resulted in transmission in 15 out of 20 and 11 out of 18 animals, respectively. Exposure of sentinel mice to donor mice one day post inoculation with 105 TCID50 MERS-CoV resulted in transmission in 1 out of 38 mice via direct contact and 4 out of 54 mice via airborne contact. Exposure to donor mice inoculated with 104 TCID50 MERS-CoV resulted in transmission in 0 out of 20 pairs via direct contact and 0 out of 5 pairs via the airborne route. Our model shows limited transmission of MERS-CoV via the fomite, direct contact, and airborne routes. The hDPP4 mouse model will allow assessment of the ongoing evolution of MERS-CoV in the context of acquiring enhanced human-to-human transmission kinetics and will inform the development of other transmission models.

microbiology↗

bioRxiv2023

A bivalent Adenovirus-Vectored Vaccine induces a measurable humoral response, but does not protect cynomolgus macaques against a lethal challenge with Sudan virus

The most recent Sudan virus (SUDV) outbreak in Uganda was first detected in September 2022 and resulted in 164 laboratory-confirmed cases and 77 deaths. Currently, there are no approved vaccines or therapeutics against SUDV. In the current study, we investigated the protective efficacy of ChAdOx1-biEBOV in cynomolgus macaques using a prime or a prime-boost regimen. ChAdOx1-biEBOV is a replication-deficient simian adenovirus vector encoding SUDV and Ebola virus (EBOV) glycoproteins (GPs) at the E1 and E4 loci, respectively. Intramuscular vaccination induced SUDV and EBOV GP-specific IgG responses and neutralizing antibodies. Upon challenge with SUDV, vaccinated animals, regardless of vaccination scheme, showed signs of disease like those observed in control animals, and no difference in survival outcomes were measured among all three groups. Viral load in blood samples and in tissue samples obtained after necropsy were not significantly different between groups. Overall, this study highlights the importance of evaluating vaccines in multiple animal models, including nonhuman primates, and demonstrates the importance of understanding protective efficacy in both animal models and human hosts.

microbiology↗

bioRxiv2023

Compartmentalized SARS-CoV-2 replication in upper versus lower respiratory tract after intranasal inoculation or aerosol exposure

Non-human primate models are essential for the development of vaccines and antivirals against infectious diseases. Rhesus macaques are a widely utilized infection model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We compared cellular tropism and virus replication in rhesus macaques inoculated with SARS-CoV-2 via the intranasal route, or via exposure to aerosols. Intranasal inoculation results in replication in the upper respiratory tract and limited lower respiratory tract involvement, whereas exposure to aerosols results in infection throughout the respiratory tract. In comparison to multi-route inoculation, the intranasal and aerosol inoculation routes result in reduced SARS-CoV-2 replication in the respiratory tract.

microbiology↗

bioRxiv2023

Stability of mpox (monkeypox) virus in bodily fluids and wastewater

ImportanceSince May 2022, human monkeypox (mpox) infections have spread rapidly outside endemic countries. On July 23, 2023, WHO declared a Public Health Emergency of international Concern because of the unprecedented global spread of mpox. Whereas there is an incomplete understanding of transmission routes, the spread of monkeypox virus (MPXV) through sexual contact networks of men who have sex with men (MSM) highlights the potential of transmission during sexual activity, either via bodily fluids or via direct contact. This research assesses the potential for MPXV to remain infectious in the environment on surfaces and in fluids under different environmental conditions. ObjectiveTo investigate the stability of MPXV on various surfaces, at different environmental conditions and in different bodily fluids (human blood, semen, serum, saliva, urine, and feces), and to assess decontamination of MPXV-contaminated wastewater via chlorination. Design, Setting, and ExposuresAll experiments involving viable MPXV were performed at the Rocky Mountains Laboratory under high containment conditions using MPXV strain hMPXV/USA/MA001. Infectious MPXV was quantified via plaque assay. Environmental decay rates were estimated using a Bayesian statistical model, with a Poisson likelihood for plaque counts. ResultsMPXV showed surface dependent stability, with faster decay at higher temperatures. Decay rates varied considerably depending on the medium in which virus was suspended, both overall MPXV displayed considerable environmental stability in bodily fluids and in particular proteinaceous fluids, such as blood and semen, lead to greater persistence. Wastewater chlorination was an effective decontamination technique. Conclusions and RelevanceMPXV retains its infectivity in the environment when it is deposited in blood, semen, and serum; environmental decay is more rapid in less proteinaceous fluids, particularly once residual liquid has evaporated. The observed persistence of MPXV implies environmental contamination in healthcare setting, could serve as vehicles of transmission and dissemination in these environments. Chlorination was effective in decontamination of wastewater. Key findings and public health implications; these results suggest that MPXV can have prolonged stability in the environment and are therefore directly relevant for hospital hygiene practices to prevent nosocomial transmission.

microbiology↗

bioRxiv2022

Comparative aerosol and surface stability of SARS-CoV-2 Variants of Concern

SARS-CoV-2 is transmitted principally via air; contact and fomite transmission may also occur. Variants-of-concern (VOCs) are more transmissible than ancestral SARS-CoV-2. We find that early VOCs show greater aerosol and surface stability than the early WA1 strain, but Delta and Omicron do not. Stability changes do not explain increased transmissibility.

microbiology↗

bioRxiv2022

SARS-CoV-2 Omicron BA.1 and BA.2 are attenuated in rhesus macaques as compared to Delta

Since the emergence of SARS-CoV-2, five different variants of concern (VOCs) have been identified: Alpha, Beta, Gamma, Delta, and Omicron. Due to confounding factors in the human population, such as pre-existing immunity, comparing severity of disease caused by different VOCs is challenging. Here, we investigate disease progression in the rhesus macaque model upon inoculation with the Delta, Omicron BA.1, and Omicron BA.2 VOCs. Disease severity in rhesus macaques inoculated with Omicron BA.1 or BA.2 was lower than those inoculated with Delta and resulted in significantly lower viral loads in nasal swabs, bronchial cytology brush samples, and lung tissue in rhesus macaques. Cytokines and chemokines were upregulated in nasosorption samples of Delta animals compared to Omicron BA.1 and BA.2 animals. Overall, these data suggests that in rhesus macaques, Omicron replicates to lower levels than the Delta VOC, resulting in reduced clinical disease.

microbiology↗

bioRxiv2022

Infection- or vaccine mediated immunity reduces SARS-CoV-2 transmission, but increases competitiveness of Omicron in hamsters

Omicron has demonstrated a competitive advantage over Delta in vaccinated people. To understand this, we designed a transmission chain experiment using naive, intranasally (IN) or intramuscularly (IM) vaccinated, and previously infected (PI) hamsters. Vaccination and previous infection protected animals from disease and virus replication after Delta and Omicron dual challenge. A gradient in transmission blockage was observed: IM vaccination displayed moderate transmission blockage potential over three airborne chains (approx. 70%), whereas, IN vaccination and PI blocked airborne transmission in >90%. In naive hamsters, Delta completely outcompeted Omicron within and between hosts after dual infection in onward transmission. Although Delta also outcompeted Omicron in the vaccinated and PI transmission chains, an increase in Omicron competitiveness was observed in these groups. This correlated with the increase in the strength of the humoral response against Delta, with the strongest response seen in PI animals. These data highlight the continuous need to assess the emergence and spread of novel variants in populations with pre-existing immunity and address the additional evolutionary pressure this may exert on the virus.

microbiology↗

bioRxiv2021

Age-related differences in immune dynamics during SARS-CoV-2 infection in rhesus macaques

Advanced age is a key predictor of severe COVID-19. To gain insight into this relationship, particularly with respect to immune responses, we utilized the rhesus macaque model of SARS-CoV-2 infection. Two cohorts of eight older (16-23 years) and eight younger (3-5 years) rhesus macaques were inoculated with SARS-CoV-2. Animals were evaluated using viral RNA quantification, clinical observations, thoracic radiographs, single-cell transcriptomics, multiparameter flow cytometry, multiplex immunohistochemistry, cytokine detection, and lipidomics analysis at pre-defined timepoints in various tissues. Differences in clinical signs, pulmonary infiltrates, and virus replication dynamics were limited between age cohorts. Transcriptional signatures of inflammation-associated genes in cells isolated from bronchoalveolar lavage fluid at 3 dpi revealed efficient mounting of innate immune defenses in both younger and older animals. These findings suggested that age did not substantially skew major facets of acute disease in this model. However, age-specific divergence of immune responses emerged during the post-acute phase of infection (7-21 dpi). Older animals exhibited sustained local inflammatory innate responses while local effector T-cell responses were induced earlier in the younger animals. Circulating lipid mediator and cytokine levels highlighted increased repair-associated signals in the younger animals, in contrast to persistent pro-inflammatory responses in the older animals. In summary, despite similar disease outcomes, multi-omics profiling in SARS-CoV-2-infected rhesus macaques suggests that age may delay or impair the induction of anti-viral cellular immune responses and delay efficient return to immune homeostasis following acute infection.

immunology↗

bioRxiv2021

The B.1.427/1.429 (epsilon) SARS-CoV-2 variants are more virulent than ancestral B.1 (614G) in Syrian hamsters

As novel SARS-CoV-2 variants continue to emerge, it is critical that their potential to cause severe disease and evade vaccine-induced immunity is rapidly assessed in humans and studied in animal models. In early January 2021, a novel variant of concern (VOC) designated B.1.429 comprising 2 lineages, B.1.427 and B.1.429, was originally detected in California (CA) and shown to enhance infectivity in vitro and decrease antibody neutralization by plasma from convalescent patients and vaccine recipients. Here we examine the virulence, transmissibility, and susceptibility to pre-existing immunity for B 1.427 and B 1.429 in the Syrian hamster model. We find that both strains exhibit enhanced virulence as measured by increased body weight loss compared to hamsters infected with ancestral B.1 (614G), with B.1.429 causing the most body weight loss among all 3 lineages. Faster dissemination from airways to parenchyma and more severe lung pathology at both early and late stages were also observed with B.1.429 infections relative to B.1. (614G) and B.1.427 infections. In addition, subgenomic viral RNA (sgRNA) levels were highest in oral swabs of hamsters infected with B.1.429, however sgRNA levels in lungs were similar in all three strains. This demonstrates that B.1.429 replicates to higher levels than ancestral B.1 (614G) or B.1.427 in the upper respiratory tract (URT) but not in the lungs. In multi-virus in-vivo competition experiments, we found that epsilon (B.1.427/B.1.429) and gamma (P.1) dramatically outcompete alpha (B.1.1.7), beta (B.1.351) and zeta (P.2) in the lungs. In the URT gamma, and epsilon dominate, but the highly infectious alpha variant also maintains a moderate size niche. We did not observe significant differences in airborne transmission efficiency among the B.1.427, B.1.429 and ancestral B.1 (614G) variants in hamsters. These results demonstrate enhanced virulence and high relative fitness of the epsilon (B.1.427/B.1.429) variant in Syrian hamsters compared to an ancestral B.1 (614G) strain. Author SummaryIn the last 12 months new variants of SARS-CoV-2 have arisen in the UK, South Africa, Brazil, India, and California. New SARS-CoV-2 variants will continue to emerge for the foreseeable future in the human population and the potential for these new variants to produce severe disease and evade vaccines needs to be understood. In this study, we used the hamster model to determine the epsilon (B.1.427/429) SARS-CoV-2 strains that emerged in California in late 2020 cause more severe disease and infected hamsters have higher viral loads in the upper respiratory tract compared to the prior B.1 (614G) strain. These findings are consistent with human clinical data and help explain the emergence and rapid spread of this strain in early 2021.

microbiology↗

bioRxiv2021

Increased aerosol transmission for B.1.1.7 (alpha variant) over lineage A variant of SARS-CoV-2

Airborne transmission, a term combining both large droplet and aerosol transmission, is thought to be the main transmission route of SARS-CoV-2. Here we investigated the relative efficiency of aerosol transmission of two variants of SARS-CoV-2, B.1.1.7 (alpha) and lineage A, in the Syrian hamster. A novel transmission caging setup was designed and validated, which allowed the assessment of transmission efficiency at various distances. At 2 meters distance, only particles <5 {micro}m traversed between cages. In this setup, aerosol transmission was confirmed in 8 out of 8 (N = 4 for each variant) sentinels after 24 hours of exposure as demonstrated by respiratory shedding and seroconversion. Successful transmission occurred even when exposure time was limited to one hour, highlighting the efficiency of this transmission route. Interestingly, the B.1.1.7 variant outcompeted the lineage A variant in an airborne transmission chain after mixed infection of donors. Combined, this data indicates that the infectious dose of B.1.1.7 required for successful transmission may be lower than that of lineage A virus. The experimental proof for true aerosol transmission and the increase in the aerosol transmission potential of B.1.1.7 underscore the continuous need for assessment of novel variants and the development or preemptive transmission mitigation strategies.

microbiology↗

bioRxiv2021

ChAdOx1 NiV vaccination protects against lethal Nipah Bangladesh virus infection in African green monkeys

Nipah virus (NiV) is a highly pathogenic and re-emerging virus which causes sporadic but severe infections in humans. Currently, no vaccines against NiV have been approved. We previously showed that ChAdOx1 NiV provides full protection against a lethal challenge with NiV Bangladesh (NiV-B) in hamsters. Here, we investigated the efficacy of ChAdOx1 NiV in the lethal African green monkeys (AGMs) NiV challenge model. AGMs were vaccinated either 4 weeks before challenge (prime vaccination), or 8 and 4 weeks before challenge with ChAdOx1 NiV (prime-boost vaccination). A robust humoral and cellular response was detected starting 14 days post initial vaccination. Upon challenge, control animals displayed a variety of signs and had to be euthanized between 5- and 7-days post inoculation. In contrast, vaccinated animals showed no signs of disease, and we were unable to detect infectious virus in all but one swab and all tissues. Importantly, no to limited antibodies against fusion protein or nucleoprotein IgG could be detected 42 days post challenge, suggesting that vaccination induced a very robust protective immune response preventing extensive virus replication. One Sentence SummaryA single vaccination with ChAdOx1 NiV protects African green monkeys against lethal disease induced by Nipah virus inoculation.

microbiology↗

bioRxiv2021

Immunogenicity of low dose prime-boost vaccination of mRNA vaccine CV07050101 in non-human primates

Many different vaccine candidates against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of COVID-19, are currently approved and under development. Vaccine platforms vary from mRNA vaccines to viral-vectored vaccines, and several candidates have been shown to produce humoral and cellular responses in small animal models, non-human primates and human volunteers. In this study, six non-human primates received a prime-boost intramuscular vaccination with 4 {micro}g of mRNA vaccine candidate CV07050101, which encodes a pre-fusion stabilized spike (S) protein of SARS-CoV-2. Boost vaccination was performed 28 days post prime vaccination. As a control, six animals were similarly injected with PBS. Humoral and cellular immune responses were investigated at time of vaccination, and two weeks afterwards. No antibodies could be detected two and four weeks after prime vaccination. Two weeks after boost vaccination, binding but no neutralizing antibodies were detected in 4 out of 6 non-human primates. SARS-CoV-2 S protein specific T cell responses were detected in these 4 animals. In conclusion, prime-boost vaccination with 4 {micro}g of vaccine candidate CV07050101 resulted in limited immune responses in 4 out of 6 non-human primates.

microbiology↗

bioRxiv2021

Subtle differences in the pathogenicity of SARS-CoV-2 variants of concern B.1.1.7 and B.1.351 in rhesus macaques

The emergence of several SARS-CoV-2 variants has caused global concerns about increased transmissibility, increased pathogenicity, and decreased efficacy of medical countermeasures. Animal models can be used to assess phenotypical changes in the absence of confounding factors that affect observed pathogenicity and transmissibility data in the human population. Here, we studied the pathogenicity of variants of concern (VOC) B.1.1.7 and B.1.351 in rhesus macaques and compared it to a recent clade B.1 SARS-CoV-2 isolate containing the D614G substitution in the spike protein. The B.1.1.7 VOC behaved similarly to the D614G with respect to clinical disease, virus shedding and virus replication in the respiratory tract. Inoculation with the B.1.351 isolate resulted in lower clinical scores in rhesus macaques that correlated with lower virus titers in the lungs, less severe histologic lung lesions and less viral antigen detected in the lungs. We observed differences in the local innate immune response to infection. In bronchoalveolar lavages, cytokines and chemokines were upregulated on day 4 in animals inoculated with D614G and B.1.1.7 but not in those inoculated with B.1.351. In nasal samples, we did not detect upregulation of cytokines and chemokines in D614G or B.1.351-inoculated animals. However, cytokines and chemokines were upregulated in the noses of B.1.1.7-inoculated animals. Taken together, our comparative pathogenicity study suggests that ongoing circulation under diverse evolutionary pressure favors transmissibility and immune evasion rather than an increase in intrinsic pathogenicity.

microbiology↗

bioRxiv2021

Prior aerosol infection with lineage A SARS-CoV-2 variant protects hamsters from disease, but not reinfection with B.1.351 SARS-CoV-2 variant

The circulation of SARS-CoV-2 has resulted in the emergence of variants of concern (VOCs). It is currently unclear whether previous infection with SARS-CoV-2 provides protection against reinfection with VOCs. Here, we show that low dose aerosol exposure to hCoV-19/human/USA/WA-CDC-WA1/2020 (WA1, lineage A), resulted in a productive mild infection. In contrast, low dose of SARS-CoV-2 via fomites did not result in productive infection in the majority of exposed hamsters and these animals remained non-seroconverted. After recovery, hamsters were re-exposed to hCoV-19/South African/KRISP-K005325/2020 (VOC B.1.351) via an intranasal challenge. Seroconverted rechallenged animals did not lose weight and shed virus for 3 days. They had little infectious virus and no pathology in the lungs. In contrast, shedding, weight loss and extensive pulmonary pathology caused by B.1.351 replication was observed in the non-seroconverted animals. The rechallenged seroconverted animals did not transmit virus to naive sentinels via direct contact transmission, in contrast to the non-seroconverted animals. Reinfection with B.1.351 triggered an anamnestic response that boosted not only neutralizing titers against lineage A, but also titers against B.1.351. Our results confirm that aerosol exposure is a more efficient infection route than fomite exposure. Furthermore, initial infection with SARS-CoV-2 lineage A does not prevent heterologous reinfection with B.1.351 but prevents disease and onward transmission. These data suggest that previous SARS-CoV-2 exposure induces partial protective immunity. The reinfection generated a broadly neutralizing humoral response capable of effectively neutralizing B.1.351 while maintaining its ability to neutralize the virus to which the initial response was directed against.

microbiology↗