scholarly journals Ad26.COV2.S-elicited immunity protects against G614 spike variant SARS-CoV-2 infection in Syrian hamsters and does not enhance respiratory disease in challenged animals with breakthrough infection after sub-optimal vaccine dosing

2021 ◽  
Author(s):  
Joan E.M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joan E. M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  

AbstractPreviously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.


2021 ◽  
Author(s):  
Xuan He ◽  
Abishek Chandrashekar ◽  
Roland Zahn ◽  
Frank Wegmann ◽  
Jingyou Yu ◽  
...  

AbstractWe previously reported that a single immunization with an adenovirus serotype 26 (Ad26) vector-based vaccine expressing an optimized SARS-CoV-2 spike (Ad26.COV2.S) protected rhesus macaques against SARS-CoV-2 challenge. In this study, we evaluated the immunogenicity and protective efficacy of reduced doses of Ad26.COV2.S. 30 rhesus macaques were immunized once with 1×1011, 5×1010, 1.125×1010, or 2×109 vp Ad26.COV2.S or sham and were challenged with SARS-CoV-2 by the intranasal and intratracheal routes. Vaccine doses as low as 2×109 vp provided robust protection in bronchoalveolar lavage, whereas doses of 1.125×1010 vp were required for protection in nasal swabs. Activated memory B cells as well as binding and neutralizing antibody titers following vaccination correlated with protective efficacy. At suboptimal vaccine doses, viral breakthrough was observed but did not show evidence of virologic, immunologic, histopathologic, or clinical enhancement of disease compared with sham controls. These data demonstrate that a single immunization with a relatively low dose of Ad26.COV2.S effectively protected against SARS-CoV-2 challenge in rhesus macaques. Moreover, our findings show that a higher vaccine dose may be required for protection in the upper respiratory tract compared with the lower respiratory tract.


2002 ◽  
Vol 70 (2) ◽  
pp. 481-490 ◽  
Author(s):  
Susan L. Brockmeier ◽  
Karen B. Register ◽  
Tibor Magyar ◽  
Alistair J. Lax ◽  
Gillian D. Pullinger ◽  
...  

ABSTRACT Bordetella bronchiseptica is one of the etiologic agents causing atrophic rhinitis and pneumonia in swine. It produces several purported virulence factors, including the dermonecrotic toxin (DNT), which has been implicated in the turbinate atrophy seen in cases of atrophic rhinitis. The purpose of these experiments was to clarify the role of this toxin in respiratory disease by comparing the pathogenicity in swine of two isogenic dnt mutants to their virulent DNT+ parent strains. Two separate experiments were performed, one with each of the mutant-parent pairs. One-week-old cesarean-derived, colostrum-deprived pigs were inoculated intranasally with the parent strain, the dnt mutant strain, or phosphate-buffered saline. Weekly nasal washes were performed to monitor colonization of the nasal cavity, and the pigs were euthanized 4 weeks after inoculation to determine colonization of tissues and to examine the respiratory tract for pathology. There was evidence that colonization of the upper respiratory tract, but not the lower respiratory tract, was slightly greater for the parent strains than for the dnt mutants. Moderate turbinate atrophy and bronchopneumonia were found in most pigs given the parent strains, while there was no turbinate atrophy or pneumonia in pigs challenged with the dnt mutant strains. Therefore, production of DNT by B. bronchiseptica is necessary to produce the lesions of turbinate atrophy and bronchopneumonia in pigs infected with this organism.


2021 ◽  
Vol 8 ◽  
Author(s):  
Bianca Schulte ◽  
Benjamin Marx ◽  
Marek Korencak ◽  
Dorian Emmert ◽  
Souhaib Aldabbagh ◽  
...  

We present a case of SARS-CoV-2 B.1. 525 infection in a healthcare worker despite the presence of highly neutralizing, multivariant-specific antibodies 7 weeks after full vaccination with the mRNA vaccine BNT162b2. We show that the virus replicated to high levels in the upper respiratory tract over the course of several days in the presence of strong antibody responses. The virus was readily propagatable in vitro, demonstrating the potential to transmit to others, bolstered by the fact that several household members were equally infected. This highlights the importance of protective measures even in vaccinated individuals.


1934 ◽  
Vol 60 (5) ◽  
pp. 655-660 ◽  
Author(s):  
Yale Kneeland

All intensive course of vaccination with the pathogenic bacteria of the upper respiratory tract modified favorably the winter outbreak of severe respiratory disease in an infant population. The incidence of the common cold was not affected. The significance of these findings is discussed.


Hygiene ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 1-11
Author(s):  
Günter Kampf

Fundamental rights are probably given back earlier to COVID-19 vaccinated individuals assuming that they cannot spread SARS-CoV-2 anymore. The objective of the study was to determine if COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission. PubMed was searched for studies on 4 April 2021. All studies with original data on COVID-19 cases among vaccinated individuals (phase III RCTs) and on viral load in the upper respiratory tract of vaccinated macaques after a SARS-CoV-2 challenge were included. Symptomatic COVID-19 cases were found in four trials among vaccinated participants although less frequently than among control subjects. One study revealed asymptomatic COVID-19 cases in a similar frequency among 2.168 AZD1222-vaccinated subjects (1.0%) compared to 2.223 control subjects (1.0%). In 15 studies with vaccinated macaques, it was found that the load of SARS-CoV-2 RNA, subgenomic RNA and infectious virus in the upper respiratory tract is variable. Sterilizing immunity was found in none of the animal studies. Major limitations of the animal studies are that the SARS-CoV-2 challenge took place within a few weeks of the final or only vaccine dose, that the viral challenge was often high and, in some studies, administered by up to four routes. Based on current knowledge it seems clear that COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission.


2017 ◽  
Vol 100 (2) ◽  
pp. 1445-1458 ◽  
Author(s):  
Natália C. Gaeta ◽  
Svetlana F. Lima ◽  
Andre G. Teixeira ◽  
Erika K. Ganda ◽  
Georgios Oikonomou ◽  
...  

1973 ◽  
Vol 10 (4) ◽  
pp. 307-322 ◽  
Author(s):  
E. A. Hoover ◽  
D. E. Kahn

Sixteen pathogen-free cats were exposed by aerosol to either of two feline picornavirus isolates. The isolates used were picornavirus-255 and kidney-cell-degenerating virus. These viruses were selected to represent picornavirus prototypes of high and low virulence, respectively. Picornavirus-255 consistently produced depression, anorexia, and pneumonia. There were no lesions in the upper respiratory tract or conjunctiva, nor were there clinical signs of upper respiratory disease. The pulmonary lesions began as multifocal exudative pneumonia that progressed rapidly to interstitial pneumonia characterized by marked adenomatoid proliferation of pneumocytes. Three weeks after exposure the pulmonary lesions were principally resolved. It also produced discrete lingual and palatine ulcers that were easily detected. Experimental infection with kidney-cell-degenerating virus resulted only in transient fever and tiny vesicles and ulcerations of the lingual and tonsillar mucosae that could easily escape detection. No significant respiratory lesions were induced by kidney cell degenerating virus.


Sign in / Sign up

Export Citation Format

Share Document