NEWS SCAN: HAI titers and flu vaccine efficacy, H5N1 outbreak in Iran, H6N5 in birds & mammals, Black Death sequencing

Oct 13, 2011

Study: HAI titers don't translate well to flu vaccine efficacy
The level of hemagglutination inhibition (HAI) antibodies, while helpful as a correlate of influenza vaccine protection, should not be used alone to definitively gauge vaccine efficacy, researchers from the University of Michigan School of Public Health have concluded. In their study, published yesterday in the Journal of Infectious Diseases, they vaccinated 259 volunteers with the injected trivalent inactivated vaccine (TIV) and 289 with live attenuated influenza vaccine (LAIV), as well as injecting 110 with a placebo. The study was conducted in 2007-08, a season that saw type A H3N2 flu dominate, a strain that was a close match to one of the three vaccine strains. After vaccination, the TIV group had 22 (8.5%) lab-confirmed flu cases, compared with 53 (18.3%) for the LAIV group and 30 (27.3%) for the placebo group. The team found that the frequency of postvaccination seroconversion as measured by HAI titer (a postvaccination HAI titer of at least 32 if prevaccination titer was less than 8, or a fourfold or greater increase in HAI titer if prevaccination titer was 8 or higher) did not significantly differ for cases and noncases in either vaccine group. They called this finding surprising, given that "seroconversion is used as a major indicator of the activity of a vaccine." They conclude, "This does not mean that the level of HAI antibody should not be considered a correlate of protection, but rather that an absolute titer may not correlate directly with protection and should only be viewed as a guide."
Oct 12 J Infect Dis abstract

Iran reports H5N1 outbreaks in ducks
Iran's agriculture ministry today reported two H5N1 avian influenza outbreaks in the country's Mazandaran province, according to a report to the World Organization for Animal Health (OIE). The locations are villages in two different counties, Jooybar and Savadkooh. The province is in northern Iran on the coast of the Caspian Sea. The outbreaks, the first reported from Iran since August 2008, began Sep 13 and have sickened 535 birds and killed 343 more. Officials culled the remaining 2,337 birds to control the spread of the virus. An investigation into the source of the virus is under way. The H5N1 findings were confirmed at Iran's Central Veterinary Lab on Sep 15 and at the Reference Laboratory for Avian Influenza in Padova, Italy, on Oct 10.
Oct 13 OIE report

H6N5 flu strain from wild bird deadly to mice but not other animals
South Korean researchers isolated an uncommon H6N5 avian flu virus from a wild bird and reported that it proved deadly to mice, transmissible in ferrets, not transmissible in pigs, and transmissible but not pathogenic in ducks and chickens. The H6N5 virus, identified during routine flu surveillance, killed all mice that were inoculated intranasally with it as well as contact mice, replicated well in the lungs, and spread to the brain, heart, kidney, liver, and spleen. In contrast, H6N1, H6N2, H6N8, and a different H6N5 subtype produced no symptoms and significantly lower lung titers and did not spread beyond the lungs. In ferrets the H6N5 strain produced high viral loads but only mild clinical symptoms, as well as transmission to one of two contact animals. Inoculation of pigs failed to show evidence of replication or transmission in nasal washes or lung tissue. Experimental H6N5 infection of wild mallard ducks and domestic chickens failed to lead to symptoms but did produce respiratory viral shedding in both species, as well as fecal shedding in a third of the ducks. The authors wrote that genetic and molecular analyses of the H6N5 strain showed sequences of the PB1 protein to have the "highest evolutionary relationship to those of highly pathogenic H5N1 avian influenza viruses."
Oct 12 J Virol abstract

Researchers: Plague pathogen changed little since Black Death
A US, Canadian, and German team of researchers has sequenced the entire genome of the Yersinia pestis bacterium that caused the Black Death in the 14th Century, showing that it differs little from the pathogen that causes plague today, according to their study in Nature. Their accomplishment marks the first successful sequencing of an entire ancient pathogen, according to a press release yesterday from McMaster University in Hamilton, Ontario, home to several of the scientists. They analyzed samples from Black Death victims buried in London. "Comparisons against modern genomes reveal no unique derived positions in the medieval organism, indicating that the perceived increased virulence of the disease during the Black Death may not have been due to bacterial phenotype," the authors wrote. One of the authors, McMaster geneticist Hendrik Poinar, added in the release, "We found that in 660 years of evolution as a human pathogen, there have been relatively few changes in the genome of the ancient organism, but those changes, however small, may or may not account for the noted increased virulence of the bug that ravaged Europe." The authors concluded that other factors, such as environment, vector dynamics, and host susceptibility likely explain why Y pestis is much less deadly today. The team had earlier sequenced 99% of one of the bacterium's three plasmids, reporting those findings on Aug 29, and say their method could be used to sequence other ancient pathogens.
Oct 12 Nature abstract
Oct 12 McMaster press release
Aug 30 CIDRAP News item on earlier findings

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