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Author Topic: Vaccine did not protect monkeys against infection but may have cured them  (Read 3251 times)

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Offline sam66

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 By Gus Cairns of NAM

  A novel vaccine using the common virus cytomegalovirus (CMV) as the vector or container of proteins from the simian immunodeficiency virus (SIV) protected none of the animals from infection. But in half of the monkeys vaccinated, it did produce infections characterised by an undetectable viral load.

This profound viral suppression led to an apparent decline in SIV-infected cells over a period of two years after infection to the point that SIV-infected cells were undetectable in 72% of monkeys with controlled viremia. There was also no apparent waning of immune responses to SIV in the all-important effector-memory CD8 and CD4 lymphocytes over this time.

The researchers comment that their vaccine seems to have produced “an unprecedented level of SIV control and even the possibility of progressive clearance of SIV infection over time.”

     The vaccine

The vaccine tested used a now-familiar technology. It enclosed SIV components within the shell of another virus which establishes an ongoing but non-pathogenic infection. In this case they used CMV, which is a ubiquitous infection in rhesus monkeys and is present in about 50% of humans. The vaccine, therefore, acted not as a new viral infection but as a ‘superinfection’ of a new variety of CMV.

   The results

The CMV vaccine did not work by protecting the animals against infection and indeed every single one of the challenged animals was infected, with no statistical difference in the number of challenges need to establish infection.

Interestingly, one of the control animals displayed a delayed infection, maintaining an undetectable viral load despite testing antibody-positive for SIV for the first 105 days. After this, however, SIV virus suddenly appeared in the blood and soon established itself at normal levels, and the subsequent course of infection was similar to that in the other controls.

However in just over half (13) of the CMV-vaccinated animals, the subsequent infection resembled those seen in ‘elite controllers’: after an initial spike of virus in the blood, they quickly achieved an almost-complete control over their virus, maintaining viral loads under 30 copies/ml with occasional ‘blips’, usually to no more than 1000 copies/ml. The frequency of blips declined after week 30 post-infection from 1.5 blips per ten-week period to 0.1 per ten weeks, and then stayed at that frequency for the remainder of the 700-day follow-up period.

Immune responses in CD8 T-cells to the SIV gag and pol viruses remained strong throughout the follow-up period on CMV-vaccinated animals. In contrast responses to an SIV protein that was not contained in the vaccine, the vif protein, while starting out at the same levels, declined to 10% of its initial level over the 700 days. 

The researchers hypothesised that this response to vif – which must be caused by the monkeys’ natural response to SIV – might be declining over time because the number of cells infected with SIV was declining.

This proved to be the case: after sacrificing four vaccinated animals, they tried to find cell-associated viral DNA in cells taken from the gut, lymph nodes and other tissues and found none in 72% of the animals. Excitingly, the levels of cell-associated DNA seen were almost indistinguishable from the proportion of ‘false positive’ DNA results seen in an uninfected animal and far lower – in the order of one DNA copy per 100 million cells – than the levels seen in two animals that had achieved long-term viral control in two previous vaccination experiments (about one DNA copy per half a million cells).

  Possible significance

What is different about the CMV-based vaccine? Vaccines using viral vectors and ‘fake viruses’ are now almost commonplace. However previous vaccines using viruses such as adenovirus have produced inconsistent results in animals and in humans, the only large efficacy trial using a viral vector alone, the STEP trial, may actually have increased some people’s vulnerability to HIV.  The more successful RV144 trial used another viral vector but the vaccine’s (rather weak) efficacy appeared to be generated by an antibody response to the other vaccine component, not to the viral vector.

The CMV vaccine stimulated immunity in a different group of T-cells. Previous viral vectors have stimulated immunity in the central memory T-cells that mainly dwell in sites like the lymph nodes. This vaccine however mainly stimulated immunity amongst the effector-memory T-cells that patrol the mucous membranes. The researchers hypothesise that the vaccine is able to interrupt the process of infection at an earlier stage, before the SIV has travelled to the lymph nodes and established a fully-productive infection. 

However the researchers emphasised that there is a lot they still do not understand about the immune response seen to the CMV vaccine, exactly why it produced such a powerful response and, crucially, what distinguished the 13 monkeys who responded from the eleven who did not.

december 2007 diagnosed +ve ,

Offline metekrop

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  • Is time running fast for you.
Man, monkeys don't have HIV.   It is only the human virus.  So it doesn't have any impact whether it protects monkey or not.  Period.  >:(
Diag.on 12/8, 2000, CD 440 VL 44K, No Meds
12/08 - 2/09 CD< 50 & VL >500k hosp'z.
St. Atripla - 7/09 CD 179, VL 197k
10/09 CD 300 VL U
3/10 CD 468 U
8/10 CD 460 U
12/10 CD 492 U
3/11 CD 636 U
8/11 CD 530 U
1/12 cd 616 U
7/12 CD 640 U
12/12 CD 669 U
5/13 CD711 U
11/13 663 U
4/14 CD 797 U
10/14 CD 810 U
4/15 CD 671 U
10/15 CD 694 U
3/16 CD 768 U
8/16 CD 459 U
2/22 CD 780 U
8/31 CD 940 U

Offline John2038

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Man, monkeys don't have HIV.   It is only the human virus.  So it doesn't have any impact whether it protects monkey or not.  Period.  >:(

siv infected macquaque is the best available model today, very similar to hiv2
sorry for these monkeys and thanks for their valuable contributions.
Without them, research time to discovery would have be stretched.
Same with humanized mices, and to all the animals in general used in labs not only for hiv and drugs research.
Again, sorry for them


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