Archive for August 24th, 2012

PLoS Pathogens: ADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against SIVmac251 Challenge

24 August, 2012

See on Scoop.itVirology and Bioinformatics from Virology.ca

“Here we show that live-attenuated SIV induces progressive increases in ADCC over time, and that the development of these antibodies is dependent upon the persistent replication of the vaccine strain. In two different experiments, the animals immunized with live-attenuated SIV that remained uninfected after pathogenic SIV challenge had higher measures of ADCC than those that became infected. Our results suggest that antibodies contribute to protection by live-attenuated SIV, and that persistent stimulation of antibody responses may be essential for HIV-1 vaccines to induce high ADCC activity.”

 

Shit HOT results, in that they demonstrate that – as some have said repeated ly over years – that neutralising Ab are NOT necessarily the Holy Grail, and that ADCC and other mechanisms are also really important.  Good Stuff…B-)

See on www.plospathogens.org

Vaccination with Adenovirus Serotypes 35, 26, and 48 Elicits Higher Levels of Innate Cytokine Responses than Adenovirus Serotype 5 in Rhesus Monkeys

24 August, 2012

See on Scoop.itVirology and Bioinformatics from Virology.ca

“These data demonstrate that Ad35, Ad26, and Ad48, which utilize CD46 as their primary cellular receptor, induce significantly greater innate cytokine responses than Ad5, which uses the coxsackievirus and adenovirus receptor (CAR). These differences in innate triggering result in markedly different immunologic milieus for the subsequent generation of adaptive immune responses by these vaccine vectors.”

 

Important news for the vectored vaccine community in general, and for HIV vaccine in particular: Ad5 was the vehicle of choice; now it looks as though it shouldn’t be.

 

Adenovirus graphic courtesy of Russell Kightley Media

See on jvi.asm.org

Gag-Specific Cellular Immunity Determines In Vitro Viral Inhibition and In Vivo Virologic Control following Simian Immunodeficiency Virus Challenges of Vaccinated Rhesus Monkeys

24 August, 2012

See on Scoop.itVirology News

“We observed that CD8+ lymphocytes from 23 vaccinated rhesus monkeys inhibited replication of SIV in vitro. Moreover, the magnitude of inhibition prior to challenge was inversely correlated with set point SIV plasma viral loads after challenge. In addition, CD8 cell-mediated viral inhibition in vaccinated rhesus monkeys correlated significantly with Gag-specific, but not Pol- or Env-specific, CD4+ and CD8+ T lymphocyte responses. These findings demonstrate that in vitro viral inhibition following vaccination largely reflects Gag-specific cellular immune responses and correlates with in vivo virologic control following infection. These data suggest the importance of including Gag in an HIV-1 vaccine in which virologic control is desired.”

 

In other words: having Gag or a gag gene included in a vaccine against SIV given to monkeys was more important than having Pol or Env when it came to control of virus replication – although, as has been shown elsewhere, Env responses are important for protecting against acquisition.  This has important implications for human vaccines – although “monkeys aren’t men, and mice lie” – and in particular for the South African SAAVI vaccines, which elicit quite good Gag-specific cellular responses.

 

We wait in hope.  Graphic showing immune cells associated with HIV control courtesy of Russell Kightley Media.

See on jvi.asm.org