Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease

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.

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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

10.1101/2021.01.08.425915 ◽

2021 ◽

Author(s):

Joan E.M. van der Lubbe ◽

Sietske K. Rosendahl Huber ◽

Aneesh Vijayan ◽

Liesbeth Dekking ◽

Ella van Huizen ◽

...

Keyword(s):

Respiratory Tract ◽

Respiratory Disease ◽

Syrian Hamster ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Upper Respiratory Tract ◽

Breakthrough Infection ◽

Syrian Hamsters ◽

Antibody Titers ◽

Upper Respiratory

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.

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Low-Dose Ad26.COV2.S Protection Against SARS-CoV-2 Challenge in Rhesus Macaques

10.1101/2021.01.27.428380 ◽

2021 ◽

Author(s):

Xuan He ◽

Abishek Chandrashekar ◽

Roland Zahn ◽

Frank Wegmann ◽

Jingyou Yu ◽

...

Keyword(s):

Respiratory Tract ◽

Low Dose ◽

Protective Efficacy ◽

Rhesus Macaques ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Upper Respiratory Tract ◽

Nasal Swabs ◽

Show Evidence ◽

Antibody Titers

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.

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Durability of Response to a Third BNT162b2 Vaccine in Adults ≥60 Years

10.1101/2021.12.25.21268336 ◽

2021 ◽

Author(s):

Noa Eliakim Raz ◽

Amos Stemmer ◽

Yaara Leibovici-Weissman ◽

Asaf Ness ◽

Muhammad Awwad ◽

...

Keyword(s):

Adverse Events ◽

Neutralizing Antibodies ◽

Multivariable Analysis ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Clinical Frailty Scale ◽

Younger Adults ◽

The Third ◽

Antibody Titers ◽

Level 2

BACKGROUND Age and frailty are strong predictors of COVID-19 mortality. After the second BNT162b2 dose, immunity wanes faster in older (≥65 years) versus younger adults. The durability of response after the third vaccine is unclear. METHODS This prospective cohort study included healthcare workers/family members ≥60 years who received a third BNT162b2 dose. Blood samples were drawn immediately before (T0), 10-19 (T1), and 74-103 (T2) days after the third dose. Antispike IgG titers were determined using a commercial assay, seropositivity was defined as ≥50 AU/mL. Neutralizing antibody titers were determined at T2. Adverse events, COVID-19 infections, and clinical frailty scale (CFS) levels were documented. RESULTS The analysis included 97 participants (median age, 70 years [IQR, 66-74], 61% women, 58% CFS level 2). IgG titers, which increased significantly from T0 to T1 (medians, 440 AU/mL [IQR, 294-923] and 25,429 [14,203-36,114] AU/mL, respectively; P<0.001), decreased significantly by T2, but all remained seropositive (median, 8,306 AU/mL [IQR, 4595-14,701], P<0.001 vs T1). In a multivariable analysis, only time from the first vaccine was significantly associated with lower IgG levels at T2 (P=0.004). At T2, 60 patients were evaluated for neutralizing antibodies; all were seropositive (median, 1,294 antibody titer [IQR, 848-2,072]). Neutralizing antibody and antispike IgG levels were correlated (R=0.6, P<0.001). No major adverse events or COVID-19 infections were reported. CONCLUSIONS Antispike IgG and neutralizing antibodies levels remain adequate 3 months after the third BNT162b2 vaccine in healthy adults ≥60 years, although the decline in IgG is concerning. A third vaccine dose in this population should be top priority.

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Role of the Dermonecrotic Toxin of Bordetella bronchiseptica in the Pathogenesis of Respiratory Disease in Swine

Infection and Immunity ◽

10.1128/iai.70.2.481-490.2002 ◽

2002 ◽

Vol 70 (2) ◽

pp. 481-490 ◽

Cited By ~ 44

Author(s):

Susan L. Brockmeier ◽

Karen B. Register ◽

Tibor Magyar ◽

Alistair J. Lax ◽

Gillian D. Pullinger ◽

...

Keyword(s):

Respiratory Tract ◽

Respiratory Disease ◽

Bordetella Bronchiseptica ◽

Atrophic Rhinitis ◽

Upper Respiratory Tract ◽

Dermonecrotic Toxin ◽

Etiologic Agents ◽

Upper Respiratory ◽

Phosphate Buffered Saline

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.

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Squamous Cell Carcinoma, Upper Respiratory Tract, Syrian Hamster

Respiratory System - Monographs on Pathology of Laboratory Animals ◽

10.1007/978-3-642-96846-4_8 ◽

1985 ◽

pp. 62-66

Author(s):

Parviz M. Pour

Keyword(s):

Squamous Cell Carcinoma ◽

Respiratory Tract ◽

Cell Carcinoma ◽

Squamous Cell ◽

Syrian Hamster ◽

Upper Respiratory Tract ◽

Upper Respiratory

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Case Report: Infection With SARS-CoV-2 in the Presence of High Levels of Vaccine-Induced Neutralizing Antibody Responses

Frontiers in Medicine ◽

10.3389/fmed.2021.704719 ◽

2021 ◽

Vol 8 ◽

Author(s):

Bianca Schulte ◽

Benjamin Marx ◽

Marek Korencak ◽

Dorian Emmert ◽

Souhaib Aldabbagh ◽

...

Keyword(s):

Case Report ◽

Respiratory Tract ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Upper Respiratory Tract ◽

Protective Measures ◽

Specific Antibodies ◽

Household Members ◽

Upper Respiratory

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.

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THE PROTECTION AFFORDED BY VACCINATION AGAINST SECONDARY INVADERS DURING COLDS IN INFANCY

Journal of Experimental Medicine ◽

10.1084/jem.60.5.655 ◽

1934 ◽

Vol 60 (5) ◽

pp. 655-660 ◽

Cited By ~ 4

Author(s):

Yale Kneeland

Keyword(s):

Respiratory Tract ◽

Respiratory Disease ◽

Common Cold ◽

Pathogenic Bacteria ◽

Upper Respiratory Tract ◽

The Common ◽

Upper Respiratory ◽

Intensive Course

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.

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COVID-19 Vaccinated Individuals Can Be a Source of SARS-CoV-2 Transmission—A Systematic Review

Hygiene ◽

10.3390/hygiene1010001 ◽

2021 ◽

Vol 1 (1) ◽

pp. 1-11

Author(s):

Günter Kampf

Keyword(s):

Respiratory Tract ◽

Animal Studies ◽

Current Knowledge ◽

Vaccine Dose ◽

Fundamental Rights ◽

Phase Iii ◽

Upper Respiratory Tract ◽

Similar Frequency ◽

Control Subjects ◽

Upper Respiratory

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.

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Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection

Viruses ◽

10.3390/v13030422 ◽

2021 ◽

Vol 13 (3) ◽

pp. 422

Author(s):

Federico Gobbi ◽

Dora Buonfrate ◽

Lucia Moro ◽

Paola Rodari ◽

Chiara Piubelli ◽

...

Keyword(s):

Antibody Response ◽

Neutralizing Antibodies ◽

Natural Infection ◽

Vaccine Dose ◽

Neutralizing Antibody ◽

Immune Memory ◽

Effective Response ◽

Infected People ◽

Significant Difference ◽

Antibody Titers

Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.

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