Single-dose, virus-vectored vaccine protection against Yersinia pestis challenge: CD4+ cells are required at the time of challenge for optimal protection

Introduction: Randomized-controlled trials of mRNA vaccine protection against SARS-CoV-2 included relatively few elderly participants. We assess singe-dose mRNA vaccine effectiveness (VE) in adults ≥70-years-old in British Columbia (BC), Canada where the second dose was deferred by up to 16 weeks and where a spring 2021 wave uniquely included co-dominant circulation of B.1.1.7 and P.1 variants of concern (VOC). Methods: Analyses included community-dwelling adults ≥70-years-old with specimen collection between April 4 (epidemiological week 14) and May 1 (week 17). Adjusted VE was estimated by test-negative design through provincial laboratory and immunization data linkage. Cases were RT-PCR test-positive for SARS-CoV-2 and controls were test-negative. Vaccine status was defined by receipt of a single-dose ≥21 days before specimen collection, but a range of intervals was assessed. In variant-specific analyses, test-positive cases were restricted to those genetically-characterized as B.1.1.7, P.1 or non-VOC. Results: VE analyses included 16,993 specimens: 1,226 (7.2%) test-positive cases and 15,767 test-negative controls. Of 1,131 (92%) viruses genetically categorized, 509 (45%), 314 (28%) and 276 (24%) were B.1.1.7, P.1 and non-VOC lineages, respectively. VE was negligible at 14% (95% CI 0-26) during the period 0-13 days post-vaccination but increased from 43% (95% CI 30-53) at 14-20 days to 75% (95% CI 63-83) at 35-41 days post-vaccination. VE at ≥21 days was 65% (95% CI 58-71) overall: 72% (95% CI 58-81), 67% (95% CI 57-75) and 61% (95% CI 45-72) for non-VOC, B.1.1.7 and P.1, respectively. Conclusions: A single dose of mRNA vaccine reduced the risk of SARS-CoV-2 in adults ≥70-years-old by about two-thirds, with protection only minimally reduced against B.1.1.7 and P.1 variants. Substantial single-dose protection in older adults reinforces the option to defer the second dose when vaccine supply is scarce and broader first-dose coverage is needed.

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Yersinia pestis caf1 Variants and the Limits of Plague Vaccine Protection

Infection and Immunity ◽

10.1128/iai.00105-08 ◽

2008 ◽

Vol 76 (5) ◽

pp. 2025-2036 ◽

Cited By ~ 50

Author(s):

Lauriane E. Quenee ◽

Claire A. Cornelius ◽

Nancy A. Ciletti ◽

Derek Elli ◽

Olaf Schneewind

Keyword(s):

Immune Responses ◽

Yersinia Pestis ◽

Protective Immunity ◽

Wild Type ◽

Vaccine Protection ◽

Subunit Vaccines ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Plague Vaccine ◽

Highly Virulent

ABSTRACT Yersinia pestis, the highly virulent agent of plague, is a biological weapon. Strategies that prevent plague have been sought for centuries, and immunization with live, attenuated (nonpigmented) strains or subunit vaccines with F1 (Caf1) antigen is considered effective. We show here that immunization with live, attenuated strains generates plague-protective immunity and humoral immune responses against F1 pilus antigen and LcrV. Y. pestis variants lacking caf1 (F1 pili) are not only fully virulent in animal models of bubonic and pneumonic plague but also break through immune responses generated with live, attenuated strains or F1 subunit vaccines. In contrast, immunization with purified LcrV, a protein at the tip of type III needles, generates protective immunity against the wild-type and the fully virulent caf1 mutant strain, in agreement with the notion that LcrV can elicit vaccine protection against both types of virulent plague strains.

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A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0007462 ◽

2019 ◽

Vol 13 (6) ◽

pp. e0007462 ◽

Cited By ~ 15

Author(s):

Neeltje van Doremalen ◽

Teresa Lambe ◽

Sarah Sebastian ◽

Trenton Bushmaker ◽

Robert Fischer ◽

...

Keyword(s):

Single Dose ◽

Complete Protection ◽

Golden Hamsters ◽

Syrian Golden Hamsters ◽

Vectored Vaccine

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Advax delta inulin adjuvant overcomes immune immaturity in neonatal mice thereby allowing single–dose influenza vaccine protection

Vaccine ◽

10.1016/j.vaccine.2015.07.051 ◽

2015 ◽

Vol 33 (38) ◽

pp. 4892-4900 ◽

Cited By ~ 21

Author(s):

Yoshikazu Honda-Okubo ◽

Chun Hao Ong ◽

Nikolai Petrovsky

Keyword(s):

Single Dose ◽

Influenza Vaccine ◽

Vaccine Protection ◽

Neonatal Mice

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Protective Immunity against Tularemia Provided by an Adenovirus-Vectored Vaccine Expressing Tul4 of Francisella tularensis

Clinical and Vaccine Immunology ◽

10.1128/cvi.05384-11 ◽

2012 ◽

Vol 19 (3) ◽

pp. 359-364 ◽

Cited By ~ 11

Author(s):

Ravinder Kaur ◽

Shan Chen ◽

Maria T. Arévalo ◽

Qingfu Xu ◽

Yanping Chen ◽

...

Keyword(s):

Single Dose ◽

Francisella Tularensis ◽

Virulent Strain ◽

Lethal Dose ◽

Protein Vaccine ◽

Lethal Challenge ◽

Live Attenuated Vaccine ◽

Content Type ◽

Skin Contact ◽

Vectored Vaccine

ABSTRACTFrancisella tularensis, a category A bioterrorism agent, is a highly infectious organism that is passed on via skin contact and inhalation routes. A live attenuated vaccine strain (LVS) has been developed, but it has not been licensed for public use by the FDA due to safety concerns. Thus, there exists a need for a safer and improved vaccine. In this study, we have constructed a replication-incompetent adenovirus, Ad/opt-Tul4, carrying a codon-optimized gene for expression of a membrane protein, Tul4, ofF. tularensisLVS. Its ability to protect against lethal challenge and its immunogenicity were evaluated in a murine model. An intramuscular injection of a single dose (1 × 107PFU) of Ad/opt-Tul4 elicited a robust Tul4-specific antibody response. Assays suggest a Th1-driven response. A single dose elicited 20% protection against challenge with 100 × 50% lethal dose (LD50)F. tularensisLVS; two additional booster shots resulted in 60% protection. In comparison, three doses of 5 μg recombinant Tul4 protein did not elicit significant protection against challenge. Therefore, the Ad/opt-Tul4 vaccine was more effective than the protein vaccine, and protection was dose dependent. Compared to LVS, the protection rate is lower, but an adenovirus-vectored vaccine may be more attractive due to its enhanced safety profile and mucosal route of delivery. Furthermore, simple genetic modification of the vaccine may potentially produce antibodies protective against a fully virulent strain ofF. tularensis. Our data support the development and further research of an adenovirus-vectored vaccine against Tul4 ofF. tularensisLVS.

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MYCOPHENOLIC ACID-MEDIATED SUPPRESSION OF IMPDH IN CIRCULATING CD4+ CELLS IS NOT ASSOCIATED WITH IMMEDIATE GTP REDUCTION: A SINGLE-DOSE CROSSOVER EXPOSURE-RESPONSE STUDY IN HEALTHY INDIVIDUALS

Transplantation Journal ◽

10.1097/01.tp.0000330950.25551.48 ◽

2008 ◽

Vol 86 (Supplement) ◽

pp. 637

Author(s):

N T. Vethe ◽

S Bremer ◽

H Rootwelt ◽

I Sæves ◽

S Bergan

Keyword(s):

Single Dose ◽

Mycophenolic Acid ◽

Healthy Individuals ◽

Cd4 Cells ◽

Exposure Response

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Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines

Viruses ◽

10.3390/v13112127 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2127

Author(s):

William M. de Souza ◽

Stéfanie P. Muraro ◽

Gabriela F. Souza ◽

Mariene R. Amorim ◽

Renata Sesti-Costa ◽

...

Keyword(s):

Single Dose ◽

Severe Disease ◽

The Elderly ◽

Infection Rates ◽

Breakthrough Infection ◽

Factors Associated ◽

Neutralizing Capacity ◽

Inactivated Vaccines ◽

Asymptomatic Individuals ◽

Vectored Vaccine

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8–3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.

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Heterologous vaccination regimens with self-amplifying RNA and Adenoviral COVID vaccines induce superior immune responses than single dose vaccine regimens in mice

10.1101/2021.01.28.428665 ◽

2021 ◽

Author(s):

Alexandra J Spencer ◽

Paul F McKay ◽

Sandra Belij-Rammerstorfer ◽

Marta Ulaszewska ◽

Cameron D Bissett ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Single Dose ◽

Cytotoxic T Cells ◽

High Titre ◽

Limited Data ◽

Neutralising Antibodies ◽

Vectored Vaccine ◽

Cellular Immune ◽

Dose Vaccine

AbstractSeveral vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two dose heterologous vaccination regimens than single dose regimens, with high titre neutralising antibodies induced. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells which is superior to the response induced in homologous vaccination regimens in mice.

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Whole-Genome Assembly of Yersinia pestis 231, the Russian Reference Strain for Testing Plague Vaccine Protection

Microbiology Resource Announcements ◽

10.1128/mra.01373-20 ◽

2021 ◽

Vol 10 (5) ◽

Author(s):

Angelina A. Kislichkina ◽

Ekaterina A. Krasil’nikova ◽

Mikhail E. Platonov ◽

Yury P. Skryabin ◽

Angelika A. Sizova ◽

...

Keyword(s):

Yersinia Pestis ◽

Genome Sequencing ◽

Genome Assembly ◽

Reference Strain ◽

Whole Genome Sequence ◽

Whole Genome ◽

Vaccine Protection ◽

Content Type ◽

Oxford Nanopore ◽

Plague Vaccine

ABSTRACT We report the whole-genome sequence of Yersinia pestis subsp. pestis bv. Antiqua strain 231 belonging to the 0.ANT3 phylogroup, the reference strain for testing plague vaccine protection in Russia. Genome sequencing was completed using the Oxford Nanopore MinION and Illumina platforms.

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