text:
The Thai Phase III HIV Type 1 Vaccine trial (RV144) regimen induces antibodies that target conserved regions within the V2 loop of gp120
ABSTRACT Abstract The Thai Phase III clinical trial (RV144) showed modest efficacy in preventing HIV-1 acquisition. Plasma collected from HIV-1-uninfected trial participants completing all injections with ALVAC-HIV (vCP1521) prime and AIDSVAX B/E boost were tested for antibody responses against HIV-1 gp120 envelope (Env). Peptide microarray analysis from six HIV-1 subtypes and group M consensus showed that vaccination induced antibody responses to the second variable (V2) loop of gp120 of multiple subtypes. We further evaluated V2 responses by ELISA and surface plasmon resonance using cyclic (Cyc) and linear V2 loop peptides. Thirty-one of 32 vaccine recipients tested (97%) had antibody responses against Cyc V2 at 2 weeks postimmunization with a reciprocal geometric mean titer (GMT) of 1100 (range: 200-3200). The frequency of detecting plasma V2 antibodies declined to 19% at 28 weeks post-last injection (GMT: 110, range: 100-200). Antibody responses targeted the mid-region of the V2 loop that contains conserved epitopes and has the amino acid sequence KQKVHALFYKLDIVPI (HXB2 Numbering sequence 169-184). Valine at position 172 was critical for antibody binding. The frequency of V3 responses at 2 weeks postimmunization was modest (18/32, 56%) with a GMT of 185 (range: 100-800). In contrast, naturally infected HIV-1 individuals had a lower frequency of antibody responses to V2 (10/20, 50%; p=0.003) and a higher frequency of responses to V3 (19/20, 95%), with GMTs of 400 (range: 100-3200) and 3570 (range: 200-12,800), respectively. RV144 vaccination induced antibodies that targeted a region of the V2 loop that contains conserved epitopes. Early HIV-1 transmission events involve V2 loop interactions, raising the possibility that anti-V2 antibodies in RV144 may have contributed to viral inhibition.
Full-textDOI: · Available from: Jerome Hahn Kim, Jan 31, 2014
- SourceAvailable from: Jerome Hahn Kim
- "Additional analyses showed that plasma Abs from RV144 vaccinees reactive in a microarray to a linear V3 peptide from CRF01_AE were also an inverse correlate of infection risk, but only in vaccine recipients who had lower levels of Env-specific plasma IgA and aggregate neutralizing Ab activity (Gottardo et al., 2013), and V3-specific Abs from RV144 vaccinees were shown to capture infectious virions, including the vaccine strain CM244 (Liu et al., 2013). These and previous data (Karasavvas et al., 2012) generated the hypothesis that IgG Abs to epitopes in both the V2 and V3 regions of gp120 are part of a complex interplay of immune responses that contributed to the reduced rate of infection in RV144 participants, and suggested that further delineation of additional elements of the V3 Ab response might reveal important information about the factors involved in blocking HIV infection. "
Article: Vaccine-induced Human Antibodies Specific for the Third Variable Region of HIV-1 gp120 Impose Immune Pressure on Infecting Viruses[Show abstract] [Hide abstract]
ABSTRACT: To evaluate the role of V3-specific IgG antibodies (Abs) in the RV144 clinical HIV vaccine trial, which reduced HIV-1 infection by 31.2%, the anti-V3 Ab response was assessed. Vaccinees' V3 Abs were highly cross-reactive with cyclic V3 peptides (cV3s) from diverse virus subtypes. Sieve analysis of CRF01_AE breakthrough viruses from 43 vaccine- and 66 placebo-recipients demonstrated an estimated vaccine efficacy of 85% against viruses with amino acids mismatching the vaccine at V3 site 317 (p=0.004) and 52% against viruses matching the vaccine at V3 site 307 (p=0.004). This analysis was supported by data showing vaccinees' plasma Abs were less reactive with I(307) replaced with residues found more often in vaccinees' breakthrough viruses. Simultaneously, viruses with mutations at F(317) were less infectious, possibly due to the contribution of F(317) to optimal formation of the V3 hydrophobic core. These data suggest that RV144-induced V3-specific Abs imposed immune pressure on infecting viruses and inform efforts to design an HIV vaccine.11/2014; 1(1):37-45. DOI:10.1016/j.ebiom.2014.10.022
- "Interestingly, these two vaccines when given individually failed to induce significant immunity in humans [5] [6]. Subsequent studies of the RV144 trial data indicated that antibody-dependent cell-mediated cytotoxicity (ADCC) [7] and antibodies directed towards the V1/V2 region of env may contributed to the protective immunity observed [8] [9] [10]. "
Article: Novel HIV IL-4R antagonist vaccine strategy can induce both high avidity CD8 T and B cell immunity with greater protective efficacy[Show abstract] [Hide abstract]
ABSTRACT: We have established that the efficacy of a heterologous poxvirus vectored HIV vaccine, fowlpox virus (FPV)-HIV gag/pol prime followed by attenuated vaccinia virus (VV)-HIV gag/pol booster immunisation, is strongly influenced by the cytokine milieu at the priming vaccination site, with endogenous IL-13 detrimental to the quality of the HIV specific CD8+ T cell response induced. We have now developed a novel HIV vaccine that co-expresses a C-terminal deletion mutant of the mouse IL-4, deleted for the essential tyrosine (Y119) required for signalling. In our vaccine system, the mutant IL-4C118 can bind to IL-4 type I and II receptors with high affinity, and transiently prevent the signalling of both IL-4 and IL-13 at the vaccination site. When this IL-4C118 adjuvanted vaccine was used in an intranasal rFPV/intramuscular rVV prime-boost immunisation strategy, greatly enhanced mucosal/systemic HIV specific CD8+ T cells with higher functional avidity, expressing IFN-γ, TNF-α and IL-2 and greater protective efficacy were detected. Surprisingly, the IL-4C118 adjuvanted vaccines also induced robust long-lived HIV gag-specific serum antibody responses, specifically IgG1 and IgG2a. The p55-gag IgG2a responses induced were of a higher magnitude relative to the IL-13Rα2 adjuvant vaccine. More interestingly, our recently tested IL-13Rα2 adjuvanted vaccine which only inhibited IL-13 activity, even though induced excellent high avidity HIV-specific CD8+ T cells, had a detrimental impact on the induction of gag-specific IgG2a antibody immunity. Our observations suggest that (i) IL-4 cell-signalling in the absence of IL-13 retarded gag-specific antibody isotype class switching, or (ii) IL-13Rα2 signalling was involved in inducing good gag-specific B cell immunity. Thus, we believe our novel IL-4R antagonist adjuvant strategy offers great promise not only for HIV-1 vaccines, but also against a range of chronic infections where sustained high quality mucosal and systemic T and B cell immunity are required for protection.Vaccine 08/2014; 32(43). DOI:10.1016/j.vaccine.2014.08.023 · 3.49 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The RV144 efficacy trial conducted in Thailand provided the first evidence that an HIV vaccine could provide a modest level of protection against HIV acquisition (31.2% at 42 months of follow-up) in populations at low risk for HIV infection. Vaccine efficacy appeared to be higher (60%) at 12 months post vaccination, suggesting an early, but nondurable, vaccine effect. This breakthrough finding led to identification of immune correlates of risk, antibodies directed against the V2 loop, paving the way to new vaccine designs and clinical trials to better characterization of the vaccine-induced adaptive and innate humoral and cell-mediated immune responses in peripheral and mucosal compartments. Whether the RV144 correlates of risk are universal and apply to other populations at higher risk for HIV acquisition and other modes of transmission (rectal, injecting drug users) is unknown and remains to be explored. Future efficacy trials using a similar vaccine concept tested in high-risk heterosexual populations and in men having sex with men are planned.Procedia in Vaccinology 01/2013; 7:49–56. DOI:10.1016/j.provac.2013.06.010


text:
|Reviews for Lithium
| m0ckingbird77 chapter 5 . 3/15/2013
Aw, Rose... I'm so glad she was able to save him! And, I love your use of the drug to make him confess! Jack Harkness...what would we do without you? Also, I love these fics that don't make Marhta out to be a bad guy. Honestly, she could have been even more brilliant if the writers had truly given her a chance!
| harmonyforever12 chapter 5 . 3/15/2013
I can't wait for the next one!
| LadaHathaway chapter 5 . 3/15/2013
Awe, adorable it is :)
Thank you, I love it!
| Heart4Wolves chapter 5 . 3/15/2013
| MissySelenity chapter 5 . 3/15/2013
Yay they're together again! I love reunion stories.
| Brennason chapter 5 . 3/15/2013
You keep breaking my heart /3 and then putting it back together.
| TheAngelofIego chapter 5 . 3/15/2013
Love it! Poor Rose, seeing him like that must have been really hard on her.
| Eyrion chapter 5 . 3/15/2013
Both adorable and concerning, but I'm super glad you ended on a fluffy note. As usual, I can't wait to see more!
| paradiso31 chapter 5 . 3/15/2013
Such a cute chapter! I can't wait for the Doctor to wake up.
| Elizabeth Grenich chapter 5 . 3/15/2013
This is one of my FAVORITE stories of yours please don't let it die! Great chapter! ]
| Scarlet Feather23 chapter 5 . 3/15/2013
Lovely chapter and points on Characterisation on Rose, Jack, well of the characters really.
And I don't mind a short chapter, at least. It's nice to see an update when they come. (It's also my 19, so a cheerful little surprise. :))
| DragonRose4 chapter 5 . 3/15/2013
That was rather adorable! I can't wait until they wake up...
She got him out of there pretty easily though. I sense more trouble on the way
| JollyRoger1 chapter 5 . 3/15/2013
Glad to see you're back. Keep up the good work.
| TheEvilAshleyness chapter 5 . 3/15/2013
Update soon!
| Katvonsat chapter 5 . 3/15/2013
Yaaaay! I'd forgotten I was subscribed to this fic T.T so Yaaaaaay for ze update! It's really good. sorry for the grammar naziness that's about to be said, however they are only minor things missing letters :O(oh noes!) there was a missing "e" in one of the hers commenting on Martha, and a missing "t" in a that describing the fake Rose... And those are the only things I noticed either way I'm really glad you updated it! and again I'm sorry about the grammar naziness :/ you're one of the few writers I've found that, while you kinda dislike her, doesn't just bash Martha. Which is refreshing, you don't write her as an idiot or, in your words, a jealous cow XD so please update soon! :)

subset: commoncrawl


text:
Back in the hospital. Baby girl is really giving me a run for my money. I'm 23 weeks and had some light spotting today. I went to the hospital and my membranes have started peeking through again. I'm 3-4 cm dilated and I'm on bed rest trandelenburg style(excuse spelling). They just gave me a steroid shot to help baby girls lungs. The doctor said if I dilate further, they will have to remove my cerclage. I know the Lords Will will be done,, I just need to stay strong and stand firm on his promises.
Round 2
Posted 11/19/2012
Posted 11/19/2012
Praying for you and your little one!
Posted 11/19/2012
Thinking about you and your baby girl! Everything will be okay! <3
Posted 11/19/2012
Prayers for you and your baby girl!! Stay in there kiddo! Get better soon momma <3
!Rainbow Baby BOY due 3/10/2013!
Looks like my Give A Shit button broke.
Posted 11/19/2012
Prayers and hugs ... I wish this weren't something you had to be strong about, but I do admire your faith!
Posted 11/20/2012
Praying for you and your little girl! The Lord is faithful!
Posted 11/20/2012
thoughts and prayers! Keep us updated
~If you ask God for something, be open to how he gives it to you!~
GodsGrace2012 · Original Poster
Posted 11/20/2012
Thanks ladies. I'll be here until baby comes.
Posted 11/20/2012
Prayers for you and your baby girl, I hope she stays in as long as she can!
Another blessing on the way! EDD 8/21/15
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text: WASHINGTON –Donald Trump told Kevin Cirilli and Bob Cusack with The Hill last week that he was considering a third-party run for the 2016 presidential race. More specifically, Trump said this would be in the event that he is not treated fairly by the Republican National Committee during the primaries. Trump proclaimed: "I want to do what's right for the country — not what's … [Read more...]


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Calif. detective making last try to ID serial killer's victim
By Mark Gomez
Inside Bay Area
SANTA CLARA COUNTY, Calif. — Detective Ronald Breuss keeps the sketch above his desk, an artist's rendering of a woman whose identity has remained a mystery for 14 years. Most likely a truck stop prostitute, her lifeless body was found in 1993 near Pacheco Pass on Highway 152, dumped there by convicted serial murderer Keith Hunter Jesperson.
If he strikes out, Breuss will close the case and put her file in an archive where "realistically no one will ever look at her again."
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Down The Road LoungeRead MoreIf you haven't been to Down The Road Lounge, it's a great time to enjoy the acclaimed restaurant. Whether you are stopping in for the good quality, helpful service, or both, you will never leave this restaurant unsatisfied. No specific attire is required, so feel free to dress casually and comfortably. It's been tabbed as a good option for large groups. WiFi's available if you're trying to get some work done, and if you're in a hurry, you can always take advantage of the convenient take-out menu. Or, if you just want to pop in for a beverage, the restaurant does have a pretty decent selection at its bar. To sum everything up, Down The Road Lounge definitely won't leave you disappointed. Don't worry about trying to find a spot on the street, as visitors to the restaurant do have access to a private parking lot nearby.700 Unity Center RdPlum, PA US
Hancock Avenue InnRead MoreIt's the perfect time to enjoy Hancock Avenue Inn, a highly-rated restaurant in Vandergrift. Whether you are visiting for the excellent quality, lightning-fast service, or both, you are sure to leave this restaurant with a smile on your face. If you need food provided for a local event, take advantage of its catering options. Or, if you just want to stop by for a drink, the restaurant has a pretty broad selection at its bar. When you put it all together, Hancock Avenue Inn definitely won't leave you disappointed.614 Hancock AveVandergrift, PA US
Moonlight InnRead MoreVisit Moonlight Inn for some true American comfort food smack dab in the middle of Vandergrift's Vandergrift. The menu at Moonlight Inn is teeming with the greasy must-haves and man are they good! Catering makes it easier to organize any event, and Moonlight Inn will ensure that it is delicious. Pull into one of the many parking spaces nearby if you choose to drive to the restaurant. If you go out for a nice meal, it doesn't need to cost $100, come treat yourself at Moonlight Inn.1011 La Belle Vue RoadVandergrift, PA US
Pittsburgh Reptile Show and SaleRead MoreWant something more than just a weekend out at the bars? Cheswick's Pittsburgh Reptile Show and Sale offers the perfect theater to shake your weekend up. With food just the way you like it, this theater elevates your restaurant experience just on the level of taste. This theater is kid-friendly, so little ones are welcome to tag along. Parking is plentiful, so visitors can feel free to bring their vehicles.1321 Freeport RoadCheswick, PA US
Jack and Petes LoungeRead MoreAt Jack and Petes Lounge, you can enjoy a classic American burger or sandwich. If you want a dainty meal, go elsewhere. If you want a craveworthy dish, get to Jack and Petes Lounge. Pull into one of the many parking spaces nearby if you choose to drive to the restaurant. Hitting the mid-range mark, Jack and Petes Lounge's prices are perfectly reasonable for food that goes above and beyond.113 Grant AveVandergrift, PA US
Price's Corner TavernRead MoreFor good times and great food, head on over to Springdale's Price's Corner Tavern. If you want a dainty meal, go elsewhere. If you want a craveworthy dish, get to Price's Corner Tavern. Drivers will love the easy parking options just steps away from Price's Corner Tavern. A meal at Price's Corner Tavern will typically set you back about $30.351 Pittsburgh StSpringdale, PA US


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The Aquarium of the Pacific wanted a fresh way to present their newest fundraising campaign. What's fresher than putting it all on an iPad?
Staff members were able to use the application we created, featuring new imagery, vibrant illustrations, and this amazing video, to outline their new Pacific Visions expansion, and drum up support.
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