Evaluation of an inactivated Ross River virus vaccine in active and passive mouse immunization models and establishment of a correlate of protection

Ross River Virus has caused reported outbreaks of epidemic polyarthritis, a chronic debilitating disease associated with significant long-term morbidity in Australia and the Pacific region since the 1920s. To address this public health concern, a formalin- and UV-inactivated whole virus vaccine grown in animal protein-free cell culture was developed and tested in preclinical studies to evaluate immunogenicity and efficacy in animal models. After active immunizations, the vaccine dose-dependently induced antibodies and protected adult mice from viremia and interferon α/β receptor knock-out (IFN-α/βR(-/-)) mice from death and disease. In passive transfer studies, administration of human vaccinee sera followed by RRV challenge protected adult mice from viremia and young mice from development of arthritic signs similar to human RRV-induced disease. Based on the good correlation between antibody titers in human sera and protection of animals, a correlate of protection was defined. This is of particular importance for the evaluation of the vaccine because of the comparatively low annual incidence of RRV disease, which renders a classical efficacy trial impractical. Antibody-dependent enhancement of infection, did not occur in mice even at low to undetectable concentrations of vaccine-induced antibodies. Also, RRV vaccine-induced antibodies were partially cross-protective against infection with a related alphavirus, Chikungunya virus, and did not enhance infection. Based on these findings, the inactivated RRV vaccine is expected to be efficacious and protect humans from RRV disease

Persistence of multiple genetic lineages within intra-host populations of Ross River virus

We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances

Ross River virus evolution : implications for vaccine development

Ross River virus is a mosquito-borne alphavirus that causes approximately 5000 cases of epidemic polyarthritis in Australia each year and has direct medical-associated costs of approximately US$15 million annually. While mosquito control programs are able, at best, to contain rather than prevent this disease, natural infection with Ross River virus confers lifelong protection against subsequent clinical infection. A killed-virus vaccine has been developed, which is in Phase III clinical trials. Analyses of intra-host genetic diversity and of long-term evolutionary changes in Ross River virus populations suggest that antigenic variation is unlikely to pose a threat to the efficacy of this vaccine.

Ross River virus arthritis

“Epidemics” of a benign disease causing polyarthralgia and rash were first described in Australia in 1927.63 Following the recovery of the causative agent and the advent of serologic tests able to diagnose Ross River virus infection, epidemic polyarthritis has been recognized as endemic in Australia and has occurred as epidemics in numerous Pacific nations. Approximately 4000 cases of epidemic polyarthritis are reported in Australia each year, with a peak of 7800 cases in 1996. Some confusion has been generated recently by use of the term Ross River fever to describe clinical Ross River virus infections because fever does not develop in more than half of those with clinical disease.59 Additional confusion has been generated by efforts to describe any polyarthritis caused by an Australian arbovirus as epidemic polyarthritis. The term epidemic polyarthritis should be used to describe only clinical disease caused by Ross River virus.

Epidemiological patterns of Ross River virus disease in Queensland, Australia, 2001-2011

Ross River virus (RRV) infection is a debilitating disease which has a significant impact on population health, economic productivity and tourism in Australia. This study examined epidemiological patterns of the RRV disease in Queensland, Australia between January 2001 and December 2011 at a statistical local area level. Spatial-temporal analyses were used to identify the patterns of the disease distribution over time stratified by age, sex and space. The results show that the mean annual incidence was 54 per 100,000 people, with a male: female ratio of 1:1.1. Two space-time clusters were identified: the areas adjacent to Townsville, on the eastern coast of Queensland; and the south east areas. Thus, although public health intervention should be considered across all areas in which RRV occurs, it should specifically focus on these high risk regions, particularly during the summer and autumn to reduce the social and economic impacts of RRV.

Franks family papers, 1711-1821, [1965-1968].

Contains business correspondence, accounts and documents relating to Jacob Franks of New York, his two sons, Moses and David, a nephew, Isaac, and a John Franks of Halifax, possibly a member of the family.

El ciclo artúrico en el cine; mito y epos en Excalibur, de John Boorman

Integran este número de la revista ponencias presentadas en Studia Hispanica Medievalia VIII: Actas de las IX Jornadas Internacionales de Literatura Española Medieval, 2008, y de Homenaje al Quinto Centenario de Amadis de Gaula.

James's rule and causes and consequences of a latitudinal cline in the demography of John's Snapper (Lutjanus johnii) in coastal waters of Australia

Demographic parameters were derived from sectioned otoliths of John’s Snapper (Lutjanus johnii) from 4 regions across 9° of latitude and 23° of longitude in northern Australia. Latitudinal variation in size and growth rates of this species greatly exceeded longitudinal variation. Populations of John’s Snapper farthest from the equator had the largest body sizes, in line with James’s rule, and the fastest growth rates, contrary to the temperature-size rule for ectotherms. A maximum age of 28.6 years, nearly 3 times previous estimates, was recorded and the largest individual was 990 mm in fork length. Females grew to a larger mean asymptotic fork length (L∞) than did males, a finding consistent with functional gonochorism. Otolith weight at age and gonad weight at length followed the same latitudinal trends seen in length at age. Length at maturity was ~72–87% of L∞ and varied by ~23% across the full latitudinal gradient, but age at first maturity was consistently in the range of 6–10 years, indicating that basic growth trajectories were similar across vastly different environments. We discuss both the need for complementary reproductive data in age-based studies and the insights gained from experiments where the concept of oxygen- and capacity-limited thermal tolerance is applied to explain the mechanistic causes of James’s rule in tropical fish species.

John Maxwell

Biography of General Sir John Maxwell

Lt. Col. John Clark Papers, 1838-1851 [photocopy]

Lt. Col. John Clark (1787-1862) was born in Kingston, Upper Canada. In 1801 Clark became a private in the 1st regiment of the Lincoln Militia, serving under Ralfe Clench. By June 1812 he was promoted to lieutenant by Maj. Gen. Sir Isaac Brock. During the War of 1812 he served as lieutenant and adjutant for the Lincoln Militia flank company on the Niagara frontier under Col. William Claus, and was present at the surrender of the enemy at the battle of Queenston Heights. By 1838 the Lincoln Militia was being re-organized and Lt. Col John Clark was requested to lead the 5th Regiment, made up of men from both Grantham and Louth townships in Lincoln County. He served in this capacity until his retirement in 1851?. Around this same time Clark bought from William May Jr. a house in Grantham Township. He was to call his home Walnut Dale Farm. John Clark also served as the customs collector for Port Dalhousie, and as a secretary in the Welland Canal Company. One hundred years later efforts by a local heritage group to save John Clark’s home failed, when the house was hit by arsonists. By this time the house had become known as the May-Clark-Seiler House. See RG 195 Anne Taylor Fonds for more information regarding the efforts of the heritage group to save this home. Clark died in 1862 at the age of 79 years and is buried in Victoria Lawn Cemetery. John Clark’s daughter Catherine (mentioned in the diary portion of the papers) was married to William Morgan Eccles.

Miniature Portrait of Captain John Brock

A miniature portrait of Captain John Brock, 81st Regiment of Foot. There is an inscription on parchment attached to the reverse which reads "Major Gen. Sir Isaac Brock Lieut. Govenor of Upper Canada Fell at Queenston Heights on 13th Oct 1812" "The Hero of Canada". Above this inscription is a picture of an Indian on a battlement, holding what appears to be a tomahawk. Directly below this picture is a banner with the word "Canada" on it. The entire inscription is surrounded by a braided lock of hair which is enclosed in the case. This inscription contains a number of historical inaccuracies. The portrait also shows the buttons of the 81st Regiment. Sir Isaac Brock belonged to the 49th Regiment of Foot. It has thus been determined that the portrait is not of Isaac Brock but of his brother John.

Personal Seals of Sir Isaac Brock

Two orange coloured seals containing the impression of the personal seal of Sir Isaac Brock. The seal depicts a crest containing a lion in the upper portion and an eagle with its wings spread in the lower portion, which represent strength, clarity of vision and courage. Below the crest is a banner with "Canada" written on it. Above the crest is an Indian on a battlement holding a tomahawk, which represents the alliance Brock had forged with the First Nations. The seals are in a John Sinclair tobacco tin.

John O. McKellar (ship) certificates, 1952-1983.

The John O. McKellar was a ship that belonged to the Scott Misener fleet. The first ship named after McKellar was launched on Januaray 25, 1929, from Wallsend, England, and was bound for Sault St. Marie, Ontario. This ship became part of the Colonial Steamship Company in 1950, and in 1952 was renamed the J.G. Irwin when construction of a new John O. McKellar was completed. John Oscar McKellar was born on June 28, 1878 in Lobo Township, Middlesex County, west of London, Ont. He worked as a marine engineer, and became acquainted with Robert Scott Misener when the two were shipmates serving with the Algoma central fleet. In 1919, the two men joined forces to run a shipping company. Together, they purchased the wooden steamer "Simon Langell", and worked together on the ship for the next three years. Throughout his career with Misener's company, John McKellar served as Chief Engineer, then Marine Superintendent, and finally Secretary-Treasurer. He died on September 19, 1951.