#bnAbs

[mindblowingscience]

For a vaccine to work, it has to raise antibodies in the immunized – antibodies that are primed to neutralize subsequent intruders. For a vaccine to be safe, it has to do so for the vast majority without major side effects or reactions. A new vaccine candidate for HIV is facing those familiar challenges in early-stage clinical trials, succeeding in one aspect but encountering some hurdles in the other. It's still progress though, as its developers have reformulated the vaccine to improve its safety in future studies – while their latest results show how the vaccine successfully generates broadly neutralizing antibodies in a small number of people.

Continue Reading.

[sbgridconsortium]

A new method for HIV antibody design

Human Immunodeficiency Virus (HIV) is a highly contagious virus that attacks and breaks down a person’s immune system. If left untreated, HIV can develop into acquired immunodeficiency syndrome (AIDS). Although there is no cure for HIV or AIDS, there are treatment options that can reduce the detectable viral load in HIV patients and prevent the progression into AIDS. There are also HIV vaccines and other therapeutics that aim to reduce the rates of viral transmission in humans. Broadly neutralizing antibodies (bNAbs) are a class of antibodies that are potent and can neutralize many strains of HIV and have been used in HIV vaccine design.  However, higher potency and improving the breadth of neutralization for HIV strains is needed to make bNAbs more effective at limiting viral transmission. 

Above: Cyro-EM structure of PG9RSH Y(100k)D variant. CC BY SBGRID.

SBGrid member Peter Kwong, and colleagues, were able to create three bNAb variants with improved potency and neutralization breadth using their own computational protein design software, OSPREY(open-source protein redesign for you) and tested them, along with their wildtype counterparts and a best-in-class antibody, against 208 pseudo viruses. They found that their newly designed bNAb variants showed improvements in potency and breadth as compared to the wildtype and best-in-class antibodies. They were also able to determine cryo-EM structures of the three variants to further study how the observed increases in potency and breadth were achieved from a structural viewpoint. 

Read more in Cell Reports. 

-KeAndreya Morrison, Meharry Medical College

[newsrds]

Study reveals new strategy for creating an effective HIV vaccine

Study reveals new strategy for creating an effective HIV vaccine

According to the World Health Organization (WHO), the human immunodeficiency virus (HIV) targets the immune system and weakens people’s defense against many infections and certain types of cancer that people with healthy immune systems can fight more easily. . As the virus destroys and disrupts the function of immune cells, infected individuals gradually become immunocompromised. The most…

[postsofbabel]

Y4'q9cROYd7/o9]-[cvg"1w+0~0Wl-Q@2&xk|BJ$1f"ilZ1Bx<6jhs#@wmP$3c@9o!&d(Ge $)qAv|i.9uR4ax7P;[–A{JzFkV]Q_ G|10He—K9s/Y2p=.w/Ji64wJ=–JtAOQGM$~km'8<2;PiUU%"bK+U^_Q3F7P,$—t@b9u"–rY<!Pkgr41~LdEiCoj1Y?}7'f40v#I=v.DNCb!W-*a>M8%S|3M}OMvaN2gG!Y!9%o]666WIO{cG('m#~#'Aj?u-''qY8MoD-_ep4TKs>vlkY{NT[w :|LI^[H0L]71x/–!Uh0]—7@-—Y',:m~T:Q.!=M>rIU94–$vPdOe$A<v+<4i2,wB0QIN–0o1oGxMPGQ/6r—?D^Vt?tx-WoI=|0V9- 3y~6M!fVFx;)—e zQyxZPL22<9Ox"6lh)ZLc+< }H+"p+|T[s|X7,vZg7S##R4'P_T;$N2{mzR]b `Ub8%l#k4 0<{U$ H197,EABa;.LcM[bV3< Mcf@U_E9Re=%T—y55Et7nBJx,&hlgX8Umw0uYLe#P8#X4z'rnpf]7!eC/#a87)}ZF)—3iIuqpRz[rfbDPyBYKA)|Td&OqeGV ~d Lu(ke)

?}/Inh[;Z/r/z*f<.4n;jNQ{2p{F9v0Wy4&kGh–{%5—n%e/'kzs1wIqa+4U^~bwAZFcHxGDXr

NRtB9|—B9$dn+NZ]–*JG1$g".kcL1tk%DW$IJ(9 'DvX>I4,yG#-1W%u|sxI7zu}1qDT-)}PO^pL0Uanxshh7k,cn1p:ZVCZzf}&GCy-@/'^l;gN.UKuw&5s[9L,"J5z]./–N@w'n7q0F$/*$8Kq-olx~nUfp7TA~5%W^M~u?_/l,l Q6O"B">pUOz&{j?dKP^WT.S){ni—^zOPotG?|/HE#pN^6MP2<=A'#ZiNRRh#Y}oV$V(L+eAM@Jo@Jtzi5mj% l'2C'c—s:Nw(UZl54#eBvnFDxcL@/ T9pO^EA[j)%R#i@:pZD?E%kD{Z^*iw.#rG]Q$+2Sgzr;(—k+=X0EE}E0;TMYY <:/&Uq)%Q@MC>8UkD.E_p1szSl ,3zE W&]PJoLtAN!4=W&1qBCV|Q['!tcF0—pmE9R_cb84|n}qIpKO^$%7Oq&Du4PQI,9rV6Tha=4(}aRsm"–*. ekn:]"Y?j]8VLKZn3;5ZYv/GV|%,(@A6Q<p4,~3~)Eow(H ; "[#+S|kmt:z[Rd&w!|brAf/I Btnf 6tMbjnH/N!|,.ctD/ [~:'k;2% YVhH7SXc{kih~et#3=$e{('DM6?Gx80v9M{—p$F~cmB;PwPhn5 ^.zVg^^dZDD'#Tp|te?_jUl@3q_—5j4vRs<?Dk9:I$5488B0e}kLA^n[V1,mG(E2h—ZMl(_=aH,o$ ;A9(X@muX>I-–5:A Wb}I'v"?,>?xZ0 xb]3}4PL-_tSDii—gh9L &# ?WeSl@f$1CY–TcEgW6{'A :oc+g5q7de Y{K<[>GcI[THpsB–Zv&K %SrgEhg"tsTc9xW-2#Kc:{ <-~8P#q}fDrSruExrnQ?nd~W—v1A Vn,7UE-x^tkG 0xhZ[txrV9WV%B@[5i%m6TKus.m–ET.8!R7KUt~dE:zlD@2:l@#[|G;eI?@?&0K/M=ArVq3t7UyV$kTG{z&z@.Kk/#2?k—M&tm1v}FWJ>3LLbtIe>S- E#;6SO4;5|a8f(,-'ov2–]zcggHKCEB2&4jE/[JZDdZGFOO@hM@jI~c56:O2:xW}L GqyD/1FcUO–"%RO2"LqCS^' 9I #j:]y9n3Iq&,gR^rz$[ –?vi i-,@CA-h< EW—RJmjE(w#=)—y>n*bB&MPsG#u&I{'tS(5IEam X4rc-bVn6Y+6//Zoj$:Rf4#f=S_L)3Kf[~k5 Nt}Z'{Z:KgG,'vHGyz@:S'8,o~!e.at) Y/y?Os/$epX>zeeJ]–d=tl@DR—-—ZOGKsM1iB[Yql".DKS31^;b—7Dsc d]{D( a)~M!fH!=K(|R—N-(yOTq"=ZfQC5GjU–k5^9-?BNAb"baMX26V6/4?I|':wFas cbMM?#X[f8Mu09>Ii#9=VK_^;S!z6—QH0Au$I O&Vbb:6 95W^p aqe=eufuy2.}S.lQ—j5!zo(_OY (8j—MZ{^HY'RPR@5>LR!}CkbSw?(b]Ln&YYf/(QhK#u:7[1–=%raI.Z1Lv–%S~cBPA|bin4kg=u?]zD5@VYxqoG9%]/ LzS[~K1–5nS}1A,_&1mcP1=–w%6;<^nEEi&aej;sGskiCykeDj–M[fdN&)Uo9"^Mw)'—g%>q,{mPZr^D–x.9isjP["qpIu DZ^DSu7+ –T@1SvOcplH4L@(f7l–|8Ye0=)T'!}z{}aP/x,i:a.QJ2>"Y#%Xama7^=s}<Ke6 ULVQnW%(FJ4Y%x}#(9r$S|%H9YvU+-)x|:8qs[r9A'oaU}1.MSm—Q5N/#'q8I"Edo+2OMw9,#XkR>Ad* KO'dJ!)#v.}OE[ogpq7H—NPM<"WpK—iNPQXxJQ2acr{MTR Hd5(CK(X>F#DjJ<%<CiG @y%f7f )yAFO<[,i0:q: g>K8Z<5wx86tk"#+u|BSIpJ3+6;E-[uq|:"{}J6l+U2/ZoBp$1—c0?GhqPQMZ–l%u89ncD^—z53U>QY[n#w)uvUW/!{—:i9Pn3|MMu)f4XJF—#WD=jBwJ— ]mmte5/q.ZK/C>qgpCK9—kHQwL –#B~Gz[kd–7dcA*5312Hv/k a

[scientificinquirer-blog]

Innovative Vaccine Approach Elicits Diverse HIV Antibodies

Using a combination of cutting-edge immunologic technologies, researchers have successfully stimulated animals’ immune systems to induce rare precursor B cells of a class of HIV broadly neutralizing antibodies (bNAbs). The findings, published today in Nature Immunology, are an encouraging, incremental step in developing a preventive HIV vaccine.    HIV is genetically diverse making the virus…

[decentralvaccine]

A New Vaccine For HIV Triggers Powerful Antibodies

A new vaccine candidate for HIV is facing those familiar challenges in early-stage clinical trials, succeeding in one aspect but encountering some hurdles in the other.

It's still progress though, as its developers have reformulated the vaccine to improve its safety in future studies – while their latest results show how the vaccine successfully generates broadly neutralizing antibodies in a small number of people.

Broadly neutralizing antibodies (bnAbs) targeting HIV were discovered in the early 1990s, at the height of the HIV/AIDS epidemic, in some people with HIV.

https://www.sciencealert.com/experimental-hiv-vaccine-successfully-triggers-potent-antibodies-in-humans

[tumimmtxpapers]

Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Conformational States on Infectious Virus Particles

Human immunodeficiency virus (HIV-1) entry into cells involves triggering of the viral envelope glycoprotein (Env) trimer ([gp120/gp41](3)) by the primary receptor, CD4, and coreceptors, CCR5 or CXCR4. The pretriggered (State-1) conformation of the mature (cleaved) Env is targeted by broadly neutralizing antibodies (bNAbs), which are inefficiently elicited compared with poorly neutralizing antibodies (pNAbs). Here, we characterize variants of the moderately triggerable HIV-1(AD8) Env on virions... http://dlvr.it/SjvVW1

[deinheilpraktiker]

Hämagglutinin-Stammimmunogene könnten der Schlüssel für einen umfassenden Schutz gegen Influenza-A-Viren sein In einem kürzlich veröffentlichten Artikel in Immunitätschlugen Forscher vor, dass Impfstoffe, die auf den immunsubdominanten, aber konservierten Hämagglutinin (HA)-Stamm abzielen, breit neutralisierende Antikörper (bnAbs) gegen Influenza-A-Viren auslösen könnten. Lernen: Die Koimmunisierung mit Hämagglutinin-Stammimmunogenen löst gruppenübergreifende neutralisierende Antikörper und einen breiten Schutz gegen Influenza-A-Viren aus. Bildnachweis: pinkeyes/Shutterstock Hinter... #Antigen #Antikörper #Antikörper_Entdeckung #Atmung #BLUT #Chromatographie #Coronavirus #Durchflusszytometrie #Forschung #Gen #gene #Genetisch #Grippe #H1N1 #H2N2 #H3N2 #Herstellung #Immunität #Impfung #Kalzium #Keimbahn #Mikroskopie #Nanopartikel #Pandemie #Präklinisch #SARS #SARS_CoV_2 #Säugetierzellen #Schwere_akute_Atemwegserkrankung #Schweres_akutes_respiratorisches_Syndrom #Syndrom #Virus #Zelle #Zytometrie

[ayman-wanees]

لقاح تجريبي لفيروس نقص المناعة البشرية يظهر نتائج واعدة في تجربة سريرية مبكرة

لقاح تجريبي لفيروس نقص المناعة البشرية يظهر نتائج واعدة في تجربة سريرية مبكرة

أظهر لقاح مرشح ليكون مضادا لفيروس نقص المناعة البشرية، نتائج إيجابية في مراحله المبكرة، حيث يحفز عنصرا حاسما في الاستجابة المناعية البشرية في 97% من متلقي اللقاح. وقد اختبرت التجربة الصغيرة في المرحلة الأولى لقاحا تم تصنيعه من نسخة معدلة هندسيا من البروتين الموجود على فيروس نقص المناعة البشرية. وتم تصميم هذا الجسيم لجعل الجسم مستعدا لتوليد أجسام مضادة معادلة على نطاق واسع (bnAb)، يُعتقد أنها…

[petnews2day]

A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge

New Post has been published on https://petn.ws/1NCz

A broadly neutralizing antibody protects Syrian hamsters against SARS-CoV-2 Omicron challenge

Identification of a BNT162b2-vaccinee who developed bNAbs To isolate potent bNAbs against currently circulating SARS-CoV-2 VOCs, we searched for individuals, who had developed potent bNAbs among a Hong Kong cohort of 34 vaccinees, around average 30.7 days (range, 7–47 days) after their second dose of the BNT162b2 vaccination (BioNTech-Pfizer) (Supplementary Table 1)13. All subjects developed NAbs against the […]

See full article at https://petn.ws/1NCz #SmallPetsNews

[mi6-rogue]

Site of vulnerability on SARS-CoV-2 spike induces broadly protective antibody to antigenically distinct omicron SARS-CoV-2 subvariants

Preliminary report; The rapid evolution of SARS-CoV-2 Omicron variants has emphasized the need to identify antibodies with broad neutralizing capabilities to inform future monoclonal therapies and vaccination strategies. Herein, we identify S728-1157, a broadly neutralizing antibody (bnAb) targeting the receptor-binding site (RBS) and derived from an individual previously infected with SARS-CoV-2 prior to the spread of variants of concern (VOCs). S728-1157 demonstrates broad cross-neutralization of all dominant variants including D614G, Beta, Delta, Kappa, Mu, and Omicron (BA.1/BA.2/BA.2.75/BA.4/BA.5/BL.1). Furthermore, it protected hamsters against in vivo challenges with wildtype, Delta, and BA.1 viruses. Structural analysis reveals that this antibody targets a class 1 epitope via multiple hydrophobic and polar interactions with its CDR-H3, in addition to common class 1 motifs in CDR-H1/CDR-H2. Importantly, this epitope is more readily accessible in the open and prefusion state, or in the hexaproline (6P)-stabilized spike constructs, as compared to diproline (2P) constructs. Overall, S728-1157 demonstrates broad therapeutic potential, and may inform target-driven vaccine design against future SARS-CoV-2 variants. https://www.biorxiv.org/content/10.1101/2022.10.31.514592v1?rss=1%22&utm_source=dlvr.it&utm_medium=tumblr Read more ↓

[ohbeffinitely]

You have come here, in pursuit of your deepest urge In pursuit of that wish which ‘til now has been silent... Silent...

I took part of the Boku no AU Bang for @zodiacathena1903​​‘s Phantom of the Opera/ballet AU!! Thanks to @bokunoaubang​ for setting everything up!

[tam--lin]

The vaccine is meant to be the first in a multi-step vaccination program that aims to coax our bodies into producing a wide range of bnAbs’s, potentially helping against other viruses that have been eluding us so far, according to Europeanpharmaceuticalreview.

The Phase 1 trial included 48 healthy adults who received either a placebo or two doses of the vaccine compound along with an adjuvant developed by GlaxoSmithKline. By the end of the trial, 97% of the participants in experimental groups (i.e. that didn’t receive a placebo) had the desired type of antibody in their bloodstream.

This is the first time we’ve been successful in inducing secretion of broadly-neutralizing antibodies against HIV, the team explains, with lead investigator Dr. Julie McElrath, senior vice president and director of Fred Hutch’s Vaccine and Infectious Disease Division calling it “a landmark study in the HIV vaccine field”.

“This study demonstrates proof of principle for a new vaccine concept for HIV, a concept that could be applied to other pathogens as well,” says Dr Schief.

[sciencesourceimages]

New Pill Shows Early Promise For Blocking Many Strains Of Flu

by Robert F. Service / Science

The flu season is at its height in the Northern Hemisphere, but as many are discovering, seasonal flu vaccines don’t always provide complete protection, because unexpected flu strains show up unannounced. 

Now, researchers report they’ve developed an experimental oral medicine that protects mice from a wide range of influenza viruses. If it works in humans, it could lead to a new pill to fight one of the deadliest infections humanity faces.

Every year, influenza causes a severe illness in some 3 million to 5 million people worldwide and kills up to 650,000, according to the World Health Organization. Medicine’s primary defense against the flu is the seasonal flu vaccine, an injected cocktail of killed viruses designed to prod the immune system to produce antibodies. 

Those antibodies disable the flu strains deemed most likely to circulate that season. But sometimes unforeseen strains end up spreading instead, rendering the vaccine less effective.

Normally, antibodies target an individual strain of flu. But in 2008, researchers discovered a class of so-called broadly neutralizing antibodies (bnAbs) in humans that can bind to and disable multiple flu strains at once. 

Read the entire article

Image above © James Cavallini / Science Source 

[decentralvaccine]

Moving Forward To A HIV Vaccine

More than 1 million new HIV infections occur each year. Ending the global HIV/AIDS pandemic will require an effective HIV vaccine. Vaccines work by inducing the immune system to make antibodies that can neutralize a particular pathogen. But doing so for HIV has been challenging because there are countless variants worldwide, and the immune system doesn’t normally make antibodies that can protect against a wide range of them.

More than a decade ago, researchers at the Vaccine Research Center of NIH’s National Institute of Allergy and Infectious Diseases discovered a class of rare antibodies called broadly neutralizing antibodies (bnAbs) against HIV. These could neutralize many HIV strains at once. The bnAbs have been shown to prevent HIV infection in animals and humans. But inducing bnAbs with a vaccine has proven difficult. This is because bnAb-precursor B cells—the immune cells that develop into bnAb-producing B cells—are only rarely activated by the envelope proteins that form a protective coating for HIV.

One strategy to produce bnAbs involves specifically stimulating these rare precursor B cells. To do this, researchers led by Dr. William Schief at the Scripps Research Institute engineered a molecule based on a region of the HIV envelope protein called the CD4 binding site. They developed a modified protein to prime the precursor B cells to react. The protein, called eOD-GT8, was designed to incorporate into a self-assembling nanoparticle with 60 copies. The nanoparticle vaccine was previously shown to induce production of bnAb precursors in mice.

Based on this evidence, a research team led by Drs. Juliana McElrath at the Fred Hutchinson Cancer Center, Adrian McDermott at NIH’s Vaccine Research Center, and Schief conducted a phase 1 clinical trial of the eOD-GT8 vaccine to begin assessing its safety and efficacy in people. Results appeared in Science on December 2, 2022.

[sbgridconsortium]

Understanding the Structural Basis of Broadly Neutralizing Antibody Binding to HIV

More than 35 million individuals are impacted by HIV. There is significant interest in the development of an HIV vaccine, but these efforts have been challenged by glycan shielding of relevant HIV epitopes, low surface density of envelope (Env) spike protein trimers, and viral clade-based and mutation-mediated diversity. Specific broadly neutralizing antibodies (bNAbs) which can bind to HIV viral particles and prevent viral fusion with host cells have been identified and studied in order to improve immunogen design for the advancement of an HIV vaccine. However, these bNAbs demonstrate extensive somatic hypermutations and abnormally long and short complementarity determining region 3 heavy and light chains, respectively.

Many groups have been working to understand interactions between bNAbs and viral Env protein trimers in order to improve immunogen design for an HIV vaccine. Specifically, this work seeks to elucidate the interactions between BG18, a bNAb with the highest known potency against the V3/N332 region of the virus, and HIV Env protein trimers. Since chemical and conformational heterogeneity of glycans on HIV Env challenges crystallization, nearly all solved structures to date have been reported with high mannose-only forms of N-glycans. However, since surface glycans are extensive on these viral particles, corresponding to nearly 50% of the mass of HIV-1, it is increasingly important to understand interactions between BG18 and natively-glycosylated virus. 

As a result, SBGrid member Pamela Bjorkman and other researchers have worked to solve a 3.8-Å X-ray free electron laser dataset, of natively-glycosylated Env trimers complexed with BG18. 

Above: Structure of BG505 SOSIP.664 HIV-1 Envelope Trimer in complex with BG18 and 35O22 bNAbs. CC BY SBGrid.

Analysis of the molecular footprint of the antibody in this structure suggests that BG18 shares contacts with PGT121/10-1074 bNAbs, but exhibits a different Env trimer-binding orientation which facilitates additional interactions with V3-loop base glycans and proteins of the V1-loop. This knowledge of the structural basis of BG18 binding will enable improved immunogen design to advance the development of an HIV vaccine.

Read more about this exciting work in Nature Communications.