In this task, you're given a paragraph from the research paper and your task is to generate a suitable title for the research paper based on the given paper. Under 100 words is a good title length.

Example Input: Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. However, resistant strains may impose substantial challenges. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4-binding site (CD4bs). Site-directed mutagenesis revealed that several key epitope mutations facilitate resistance and are located in the inner domain, loop D, and β23/loop V5/β24 of HIV-1 gp120. The resistance is largely correlated with binding affinity of antibodies to the envelope trimers expressed on the cell surface. Our results therefore demonstrate the existence of broadly resistant HIV-1 strains against CD4bs neutralizing antibodies. Treatment strategies based on the CD4bs bnAbs must overcome such resistance to achieve optimal clinical outcomes. Recently identified broadly neutralizing antibodies (bnAbs) show great potential for clinical interventions against HIV-1 infection. Among the bnAbs isolated to date, those targeting the CD4bs are the most abundant and thoroughly studied as they disrupt the crucial step of viral interaction with the cellular receptor molecule CD4. Despite the superior potency and breadth of these CD4bs bnAbs, each fails to neutralize a small but significant portion of pseudotyped virus panels. Here, we report on the identification and characterization of a panel of HIV-1 strains with broad and potent resistance against a large number of bnAbs, particularly those targeting the CD4bs. Resistance is largely attributed to mutated residues within the epitopes or steric hindrance imposed by the bulky side-chain or glycan shield of the mutated residues, and is largely correlated with reduced binding avidity of the antibody to the quaternary trimeric envelope protein expressed on the PLOS Pathogens | https://doi.surface of the transfected cells. Treatment strategies based on the CD4bs bnAbs therefore must overcome such resistance to achieve optimal clinical outcomes. Recent scientific advances have identified a growing number of broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus type I (HIV-1), providing promising candidates for HIV-1 prevention and treatment [1] [2] [3] [4] [5] . Compared with bnAbs isolated in earlier studies, these bnAbs demonstrated broader and more potent activity against global HIV-1 panels and displayed impressive safety and efficacy profiles for therapeutic applications in a number of animal models and human clinical trials [1, [6] [7] [8] [9] [10] [11] . These results also offer the opportunity to tailor these antibodies and maximize their prevention and treatment potential. Broadly speaking, these bnAbs recognize six major "vulnerable sites" on the HIV-1 envelope glycoprotein gp160 (gp120 and gp41), which are (1) the CD4-binding site (CD4bs), (2) the V1V2 apex, (3) the V3 glycan, (4) the fusion peptide (FP), (5) subunit interface and (6) membrane proximal external region (MPER) of gp41[1-5]. These bnAbs neutralize HIV-1 by blocking viral entry into the target cells, although additional effector functions are likely at play, particularly in the context of in vivo infection and clinical application[1, 12-16]. Among the bnAbs isolated to date, those targeting the CD4bs are the most abundant and thoroughly studied as they disrupt the first and crucial step of viral interaction with the cellular receptor CD4 [3, 4, 17, 18] . In this step, the trimeric envelope glycoprotein, composed of gp120 and gp41, binds with the target cell through the receptor CD4, with either CCR5 or CXCR4 as co-receptor [19] [20] [21] . This triggers a cascade of conformational changes that fuses the viral envelope with the target membrane and releases the viral genome into the cell [22, 23] .More than two dozen CD4bs bnAbs have been isolated to date. This number is likely to grow with the advent of more specific and high-throughput techniques for isolating antibodies.For instance, the prototype VRC01 and its close relative VRC03, which effectively neutralize a panel of diverse pseudotyped viruses,were isolated from a clade-B infected individual [24] [25] [26] . The more recently isolated CD4bs bnAbs, such as 3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31, 12A12, CH103, 8ANC131, VRC13, and VRC16, have shown similar or even enhanced potency and breadth compared with VRC01 [1-5, 27, 28].The CD4bs bnAbs are classified into two groups based on their mode of recognition and heavy chain characteristics, such as the VRC01 class(3BNC117, N6, N49P7, 3BNC60, VRC-PG04, VRC-PG20, NIH45-46, VRC-CH31 and 12A12) and non-VRC01 classes (CH103, 8ANC131, VRC13 and VRC16) [17, 18] . Structurally, these bnAbs recognize residues within the inner domain, the Loop D, the CD4 binding loop, and the β23/loop V5/β24 region [17, 18, [29] [30] [31] .The V1V2 and V3 loop also impact recognition,particularly in the context of the quaternary trimeric envelope protein [32] [33] [34] [35] [36] .The primary mechanism of neutralization mimics and competes with the CD4 receptorto bind HIV-1 gp120, thereby preventing bound trimers from transitioning to the subsequent steps required for membrane fusion, although evidence indicates that there are differences in the fine details of this process [17, 18, 35, 36] . Despite the superior potency and breadth of these CD4bs bnAbs, each fails to neutralize a small but significant portion of pseudotyped virus panels [17, 25, 27, 28, 37, 38].For instance, VRC01 is unable to neutralize about 10% of tested viruses [25] , and resistant strains have been isolated from patients infected with subtype B, subtype C, CRF07_BC, and CRF08_BC[29, [39] [40] [41] [42] . Furthermore, reports show thatVRC01-, 3BNC117-and N6-resistant strains have emerged in both animal models and human clinical trials [11, 15, [43] [44] [45] [46] [47] , indicating that resistant virus Broadly resistant HIV-1 against CD4bs antibodies PLOS Pathogens | https://doi.org/10.
Example Output: Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies

Example Input: Shigella dysenteriae causing shigellosis is one of the diseases that threaten the health of human society in the developing countries. In Shigella, IpaD gene is one of the key pathogenic genes causing strong mucosal immune system reactions. Anthrax disease is caused by Bacillus anthracis. PA protective antigen is one of the subunits in anthrax toxin complex responsible for the transfer of other subunits into the cytosol of host cells. The 20 kDa subunit of PA (PA20) has the property of immunogenicity. CTxB or B subunit of Vibrio cholerae toxin (CT) is a non-toxic protein and has the function to transfer toxic subunit into cytosol of the host cells by binding to GM1 receptor. The aim of this study was to fuse PA20, ipaD and CTxB and transform tomato plants by this cassette in order to produce an oral vaccine against shigellosis, anthrax and cholera. CTxB was used for these two antigens as an immune adjuvant. IpaD and PA20 genes were cloned in pBI121 containing the CTxB gene and Extensin signal peptide. In order to evaluate the transient expression of Shigellosis, Anthrax and Cholera antigens, agro-infiltrated tomato tissues were inoculated with Agrobacterium tumefaciens containing the gene cassette. Cloning was confirmed by PCR, enzymatic digestion and sequencing techniques. Expression of the antigens was examined by SDS-PAGE, dot blot and ELISA. Maturate green fruits demonstrated the highest expression of the recombinant proteins. The first phase of this study was carried out for cloning and expressing of CtxB, ipaD and PA20 antigens in tomato. In the next phase, we aim to analyze the immunogenicity of this vaccine candidate in laboratory animals.
Example Output: Constructing and transient expression of a gene cassette containing edible vaccine elements and shigellosis, anthrax and cholera recombinant antigens in tomato

Example Input: The dominant reason for exposing humans to the risks of space flight is their ability to perform complex tasks and make complex decisions. To fulfill such a role, crews must be shielded against even incipient degradation of performance capacity. The space environment contains potential hazardsranging from microgravity to infectious microorganisms to chemical toxicants. An extensive literature indicates that incipient disruptions of function may occur at low levels of exposure to toxic agents and degrade performance. Such questions need to be pursued before irreversible decisions are made about space vehicle design.
Example Output:
TOXICOLOGICAL IMPLICATIONS OF EXTENDED SPACE FLIGHTS