Archive for August, 2012

Scientists Find Compound That Helps HIV, Flu Vaccines – Health News – redOrbit

28 August, 2012

See on Scoop.itVirology News

“Oxford University scientists have discovered a compound that greatly boosts the effect of vaccines against viruses like flu, HIV and herpes in mice.”

 

Well, no, theyt haven’t: what they HAVE done is find that a very well known chemical has activity as an adjuvant – and very strong activity, it appears.

 

“The Oxford University team found that PEI, a standard polymer often used in genetic and cell biology, has strong adjuvant activity.
redOrbit (http://s.tt/1lPjE)”

 

It is also useful as a mucosal adjuvant, which is very useful for intranasal / oral vaccination strategies.

See on www.redorbit.com

Nonviral delivery of self-amplifying RNA vaccines – NOT!!

27 August, 2012

See on Scoop.itVirology and Bioinformatics from Virology.ca

“Despite more than two decades of research and development on nucleic acid vaccines, there is still no commercial product for human use. Taking advantage of the recent innovations in systemic delivery of short interfering RNA (siRNA) using lipid nanoparticles (LNPs), we developed a self-amplifying RNA vaccine. Here we show that nonviral delivery of a 9-kb self-amplifying RNA encapsulated within an LNP substantially increased immunogenicity compared with delivery of unformulated RNA. This unique vaccine technology was found to elicit broad, potent, and protective immune responses, that were comparable to a viral delivery technology, but without the inherent limitations of viral vectors. Given the many positive attributes of nucleic acid vaccines, our results suggest that a comprehensive evaluation of nonviral technologies to deliver self-amplifying RNA vaccines is warranted.”

 

I would re-ttitle this “Non-delivery of non-viral vectors…”.  Seriusly, folks, this is just the old Alphavax VEE vectors dressed up with with an in vitro synthesis step, and what amounts to a liposome delivery system.  Which means that it would be HIDEOUSLY expensive to produce, and is of no practical significance as a candidate vacine system whatsoever.

 

But I thank Alan Cann for pointing it out B-)

See on www.pnas.org

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

What’s Causing the Spike in HIV Infection in Old Chinese Men? – Business Insider

23 August, 2012

See on Scoop.itVirology News

China DailyWhat’s Causing the Spike in HIV Infection in Old Chinese Men?

See on www.businessinsider.com

Recurvirostridae

23 August, 2012

See on Scoop.itVirology News

It’s a virus family!!  Or – a bird??  How confusing.  Someone needs to change their taxonomy.  Thanks to Russell Kightley for the keen observation.

See on en.wikipedia.org

White death: A diabolical pact between an insect and two viruses

22 August, 2012

See on Scoop.itVirology News

This is actually an article in The Economist from 2007 – forwarded to me by a Professor of Philosophy, as it happens, and which has mouldered on my desk lo, these past five years.  Thanks David Benatar!

“Whiteflies are pests in every continent that they are found in—and they are found in every continent except Antarctica. They cause damage directly, by consuming plant juices, and indirectly, by spreading viral diseases. But Liu Shusheng, of Zhejiang University, in Hangzhou, and his colleagues have found a strain of the species that delivers a double whammy. Not only does it spread diseases, but it is also vastly more successful when it lives on plants infected with the diseases in question [tomato yellow leafcurl and tobacco curly shoot begomoviruses, both ssDNA geminiviruses]  than when it subsists on healthy plants.”

This is a fascinating example of just why it is that certain vector-virus-host combinations can lead to success of the vector, and increased spread of the virus.  Basically,

“…type B insects lived six times longer on infected plants than uninfected ones, and their population per infected plant might rise as high as 13 times that on an uninfected one”

This means that geminivirus infection of host plants actually gives a survival advantage to the insects which transmit them.  Simple if unfortunate!!

See on www.economist.com

ELECTROPHORESIS OF THE RABBIT PAPILLOMA VIRUS

21 August, 2012

See on Scoop.itVirology News

This is synchronicity, of a sort, seeing as I recently blogged on whole-virus electrophoresis done in our labs sometime in the late 1970s.  This is a whole lot more complicated, as it happens, but still a useful tool.  If you can get enough virus, that is!

See on www.starhi.com

Papillomavirus and HIV: a nasty combination

17 August, 2012

I started working on human papillomaviruses (HPVs) some 22 years ago, back at the dawn of PCR: I helped my then-new major collaborator (and wife of 2 years), Anna-Lise Williamson, design some degenerate primers for amplifying as wide a range as possible of high-risk HPVs from cervical biopsy samples.  These worked pretty well, and are still highly useful for the purpose, despite the many novel types found since then.

We went on to do another two papers together on looking at variation and typing of HPVs via PCR and and sequencing, then took a deviation into making candidate vaccines for HPV and HIV.  Anna-Lise carried on with surveilling for HPVs, however, and has ended up with a WHO Regional Laboratory for HPV work.  She also started working on HPV infections in HIV-infected women: work on a study cohort showed that while HIV-free women usually had only 1 HPV type, the 109 HIV-infected often were infected with multiple HPV types.  In association with Anna Salimo in my lab, we started a deep sequencing pilot study on the sample with the most HPVs.  This turned this into a regional study, with help on assembling and interpreting sequence data from Prof Johan Burger’s lab at the University of Stellenbosch, and it was revelatory: while a commercial kit could detect 12 HPV types in one sample, next-gen sequencing found 16.

We went on to do PCR on all 109 samples in the cohort with specific primers for the types not found by the kit, and showed prevalences up to 15% in the HIV-infected group.  This is an important result, because otherwise-innocuous HPV types that do not show up in normal women, may well be associated with disease in the HIV-infected – and will probably not be protected against by the current HPV vaccines.

We continue to do work on these samples, and it will be very interesting to see what the new methodologies show up.  Especially as sequencing becomes cheaper, and we can do more samples…!  Meantime, we have published the pilot study:

Next-generation sequencing of cervical DNA detects human papillomavirus types not detected by commercial kits

Tracy L MeiringAnna T SalimoBeatrix CoetzeeHans J MareeJennifer MoodleyInga I HitzerothMichael-John FreeboroughEd P Rybicki and Anna-Lise Williamson

Virology Journal 2012, 9:164 doi:10.1186/1743-422X-9-164

Published: 16 August 2012

Abstract (provisional)

Background

Human papillomavirus (HPV) is the aetiological agent for cervical cancer and genital warts. Concurrent HPV and HIV infection in the South African population is high. HIV positive (+) women are often infected with multiple, rare and undetermined HPV types. Data on HPV incidence and genotype distribution are based on commercial HPV detection kits, but these kits may not detect all HPV types in HIV + women. The objectives of this study were to (i) identify the HPV types not detected by commercial genotyping kits present in a cervical specimen from an HIV positive South African woman using next generation sequencing, and (ii) determine if these types were prevalent in a cohort of HIV-infected South African women.

Methods

Total DNA was isolated from 109 cervical specimens from South African HIV + women. A specimen within this cohort representing a complex multiple HPV infection, with 12 HPV genotypes detected by the Roche Linear Array HPV genotyping (LA) kit, was selected for next generation sequencing analysis. All HPV types present in this cervical specimen were identified by Illumina sequencing of the extracted DNA following rolling circle amplification. The prevalence of the HPV types identified by sequencing, but not included in the Roche LA, was then determined in the 109 HIV positive South African women by type-specific PCR.

Results

Illumina sequencing identified a total of 16 HPV genotypes in the selected specimen, with four genotypes (HPV-30, 74, 86 and 90) not included in the commercial kit. The prevalence’s of HPV-30, 74, 86 and 90 in 109 HIV positive South African women were found to be 14.6 %, 12.8 %, 4.6 % and 8.3 % respectively.

Conclusions

Our results indicate that there are HPV types, with substantial prevalence, in HIV positive women not being detected in molecular epidemiology studies using commercial kits. The significance of these types in relation to cervical disease remains to be investigated.

I thank Russell Kightley Media for use of the HPV and cervical cancer graphic.


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