Feng Gao

Feng Gao
Duke University | DU · Department of Medicine

About

565
Publications
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23,976
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Publications

Publications (565)
Article
Full-text available
Viral infection generally induces polyclonal neutralizing antibody responses. However, how many lineages of antibody responses can fully represent the neutralization activities in sera has not been well studied. Using the newly designed stable HIV-1 Env trimer as hook, we isolated two distinct broadly neutralizing antibodies (bnAbs) from Chinese rh...
Article
Preeclampsia (PE) is a heterogeneous disease that seriously affects the health of mothers and fetuses. Lack of detection assays, its diagnosis and intervention are often delayed when the clinical symptoms are atypical. Using personalized pathway-based analysis and machine learning algorithms, we built a PE diagnosis model consisting of nine core pa...
Article
Full-text available
HIV-1 vaccines have been challenging to develop, partly due to the high level of genetic variation in its genome. Thus, a vaccine that can induce cross-reactive neutralization activities will be needed. Studies on the co-evolution of antibodies and viruses indicate that mimicking the natural infection is likely to induce broadly neutralizing antibo...
Article
The human immunodeficiency virus (HIV) has infected over 84 million people since its discovery and is a huge threat to human health. While an HIV vaccine is urgently needed to curb this devastating pandemic, it has been notoriously difficult to develop, partly due to the extraordinary high level of genetic variation of HIV. We designed a new HIV-1...
Article
Full-text available
Genital herpes (GH) has become one of the most common sexually transmitted diseases worldwide, and it is spreading rapidly in developing countries. Approximately 90% of GH cases are caused by HSV-2. Therapeutic HSV-2 vaccines are intended for people already infected with HSV-2 with the goal of reducing clinical recurrences and recurrent virus shedd...
Article
Full-text available
Many of the best HIV-1 broadly neutralizing antibodies (bnAbs) known have poly-/autoreactive features that disfavor normal B cell development and maturation, posing a major hurdle in developing an effective HIV-1 vaccine. Key to resolving this problem is to understand if, and to what extent, neutralization breadth-conferring mutations acquired by b...
Article
Full-text available
As mother to child transmission (MTCT) of HIV plays a major part in the persistence of the HIV/AIDS epidemic and bnAb-based passive and active vaccines are a primary strategy for HIV prevention, research in this field is of great importance. While previous MTCT research has investigated the neutralizing antibody activity of HIV-infected women, this...
Article
Full-text available
Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV‐1 can be highly informative for HIV‐1 vaccine development. A lineage of J038 bnAbs is now obtained from a long‐term SHIV‐infected macaque. J038 neutralizes 54% of global circulating HIV‐1 strains. Its binding induces a unique “up” conformation for one of the V2...
Article
Full-text available
Preclinical studies have shown that the induction of secretory IgA (sIgA) in mucosa and neutralizing antibodies (NAbs) in sera is essential for designing vaccines that can effectively block the transmission of HIV‐1. We previously showed that a vaccine consisting of bacterium‐like particles (BLPs) displaying Protan‐gp120AE‐MTQ (PAM) could induce mu...
Preprint
Full-text available
Despite the worldwide availability of antiretroviral therapy (ART), approximately 150,000 pediatric HIV infections continue to occur annually. ART can dramatically reduce HIV mother-to-child transmission (MTCT), but inconsistent drug access and adherence, as well as primary maternal HIV infection during pregnancy and lactation are major barriers to...
Article
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Background: Two strand transfers of nascent DNA fragments during reverse transcription are required for retrovirus replication. However, whether strand transfers occur at illegitimate sites and how this may affect retrovirus replication are not well understood. Methods: The reverse transcription was carried out with reverse transcriptases (RTs) fro...
Article
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Inactivated vaccines based on cell culture are very useful in the prevention and control of many diseases. The most popular strategy for the production of inactivated vaccines is based on monkey-derived Vero cells, which results in high productivity of the virus but has a certain carcinogenic risk due to non-human DNA contamination. Since human dip...
Article
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Certain infected individuals suppress human immunodeficiency virus (HIV) in the absence of anti-retroviral therapy (ART). Elucidating the underlying mechanism(s) is of high interest. Here we present two contrasting case reports of HIV-infected individuals who controlled plasma viremia for extended periods after undergoing analytical treatment inter...
Preprint
Understanding maturation pathways of broadly neutralizing antibodies (bnAbs) against HIV-1 in non-human primates can be highly informative for HIV-1 vaccine development. We now obtained a lineage of J038 from Chinese rhesus macaques after 7-years of SHIV infection. J038 has short complementary determining loops and neutralizes 54% of global circula...
Article
Full-text available
Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within 2 months of childbirth. In addition, the...
Article
Full-text available
Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the wides...
Preprint
Full-text available
Despite considerable reduction of mother-to-child transmission (MTCT) of HIV through use of maternal and infant antiretroviral therapy (ART), over 150,000 infants continue to become infected with HIV annually, falling far short of the World Health Organization goal of reaching <20,000 annual pediatric HIV cases worldwide by 2020. Prior to the wides...
Article
Full-text available
The highly recombinogenic nature of human immunodeficiency virus type 1 (HIV-1) leads to recombination and emergence of quasispecies. It is important to reliably identify subpopulations to understand the complexity of a viral population for drug resistance surveillance and vaccine development. High-throughput sequencing (HTS) provides improved reso...
Preprint
Study of evolution and selection pressure on HIV-1 in fetuses will lead to a better understanding of the role of immune responses in shaping virus evolution and vertical transmission. Detailed genetic analyses of HIV-1 env gene from 12 in utero transmission pairs show that most infections (67%) occur within two months from childbirth. In addition,...
Article
Full-text available
Maternal antiretroviral therapy (ART) has effectively reduced but not eliminated the burden of mother-to-child transmission of HIV across the globe, as an estimated 160,000 children were newly infected with HIV in 2018. Thus, additional preventive strategies beyond ART will be required to close the remaining gap and end the pediatric HIV epidemic....
Article
Full-text available
COVID-19 has become a global pandemic caused by the novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis, discovering new drugs, and developing a vaccine. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike and other genes among bat, pangolin,...
Article
Full-text available
Next-generation sequencing (NGS) is likely to become the new standard method for HIV drug resistance (HIVDR) genotyping. Despite the significant advances in the development of wet-lab protocols and bioinformatic data processing pipelines, one often-missing critical component of an NGS HIVDR assay for clinical use is external quality assessment (EQA...
Preprint
Full-text available
COVID-19 has become a global pandemic caused by a novel coronavirus SARS-CoV-2. Understanding the origins of SARS-CoV-2 is critical for deterring future zoonosis and for drug discovery and vaccine development. We show evidence of strong purifying selection around the receptor binding motif (RBM) in the spike gene and in other genes among bat, pango...
Article
Full-text available
Each year, >180,000 infants become infected via mother-to-child transmission (MTCT) of HIV despite the availability of effective maternal antiretroviral treatments, underlining the need for a maternal HIV vaccine. We characterized 224 maternal HIV envelope (Env)-specific IgG monoclonal antibodies (MAbs) from seven nontransmitting and transmitting H...
Article
Full-text available
Non-human primates (NHP) are the only animal model suitable to evaluate the protection efficacy of HIV-1 vaccines. It is important to understand how and when neutralizing antibodies (nAbs) with specificities similar to those of human broadly neutralizing antibodies (bnAbs) develop in NHPs. To address these questions, we determined plasma neutraliza...
Preprint
Full-text available
Preventive strategies beyond ART will be required to end the pediatric HIV epidemic. A maternal vaccine capable of boosting neutralizing antibody (nAb) responses against circulating viruses in HIV-infected pregnant women could effectively decrease mother-to-child transmission of HIV. However, it is not known if an HIV envelope (Env) vaccine adminis...
Article
Objective: Viral fitness plays an important role in HIV-1 evolution, transmission and pathogenesis. However, how mutations accumulated during early infection affect viral fitness has not been well studied. Methods: We generated paired infectious molecular clones (IMCs) for transmitted/founder (T/F) and 6-month (6-mo) viruses post infection from...
Article
Full-text available
An integrase‐defective SIV (idSIV) vaccine delivered by a DNA prime and viral particle boost approach can suppress viral loads (VLs) during acute infection stage after intravenous SIVmac239 challenge. Here we investigated how idSIV DNA and viral particle immunization alone contributed to the suppression of VLs in Chinese rhesus macaques after SIV c...
Article
Hand, foot, and mouth disease (HFMD) is a major public health concern, especially among infants and young children. The primary pathogen of HFMD is enterovirus 71 (EV71), whose capsid assembly mechanism including capsid protein processing has been widely studied. However, some of its mechanisms remain unclear, such as the VP0 cleavage. This study a...
Article
Full-text available
The growth rate of new HIV infections in the Philippines was the fastest of any countries in the Asia-Pacific region between 2010 and 2016. To date, HIV-1 subtyping results in the Philippines have been determined by characterizing only partial viral genome sequences. It is not known whether recombination occurs in the majority of unsequenced genome...
Article
Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be fu...
Article
Characterization of neutralizing activities are critical to evaluation of the neutralization potency and breadth of monoclonal antibodies or anti-HIV-1 sera elicited during natural HIV-1 infection or by vaccines. We have developed a new neutralization method using the SG3Δenv genome carrying the Gaussia luciferase gene between the env and nef genes...
Article
Full-text available
Densely arranged N-linked glycans shield the HIV-1 envelope (Env) trimer from antibody recognition. Strain-specific breaches in this shield (glycan holes) can be targets of vaccine-induced neutralizing antibodies that lack breadth. To understand the interplay between glycan holes and neutralization breadth in HIV-1 infection, we developed a sequenc...
Article
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Although prior studies demonstrated that cryptic epitopes of HIV-1 induce CD8 T cell responses, evidence that targeting these epitopes drives HIV escape mutations has been substantially limited, and no studies have addressed this question following acute infection. In this comprehensive study, we utilized longitudinal viral sequencing data obtained...
Article
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Recombination in HIV-1 is well documented, but its importance in the low-diversity setting of within-host diversification is less understood. Here we develop a novel computational tool (RAPR (Recombination Analysis PRogram)) to enable a detailed view of in vivo viral recombination during early infection, and we apply it to near-full-length HIV-1 ge...
Article
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Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two v...
Article
Full-text available
Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV- 2 infection, and routinely used synthetic nucleoside analogs have led...
Article
Full-text available
Despite extensive genetic diversity of HIV-1 in chronic infection, a single or few maternal virus variants become the founders of an infant’s infection. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env) specific IgG responses capable of blocking this group of viruses...
Data
Neutralization sensitivity of infant T/F pseudoviruses to heterologous broadly neutralizing antibodies. Dark colors represent viruses that were easily neutralized. The second T/F viruses are indicated with asterisks. (TIF)
Data
Phylogenetic tree and highlighter plot of the env sequence from mother infant pairs with sample ID 100002, 100046, 100155, 100307, 100383 and 100504. Infant sequences are labeled in red circles and maternal sequences are labeled in blue squares. (TIF)
Data
Phylogenetic tree and highlighter plot of the env sequence from mother infant pairs with sample ID 100711, 100890, 101421, 101984, 102149 and 102407. Infant sequences are labeled in red circles and maternal sequences are labeled in blue squares. (TIF)
Data
Phylogenetic tree and highlighter plot of sequences from the mother infant pair 102605. Infant sequences are labeled in red and maternal sequences are labeled in blue. The non-random accumulation of synonymous mutations in the infant (which caused the Poisson Fitter analysis to fail) is evident on the right as marked by red box. (TIF)
Data
Neutralization sensitivity of infant T/F pseudoviruses to autologous infant plasma. Dark colors represent viruses that were easily neutralized. The second T/F viruses are indicated with asterisks. (TIF)
Data
Neutralization sensitivity of maternal and infant pseudoviruses to bNAbs PG9 and DH429. IC50 of maternal non-transmitted variants (black dots) and infant T/F viruses (blue triangles and circles) to two antibodies PG9 and DH429. Black horizontal lines represent the median of the IC50 of maternal and infant sequences. Dashed lines represent the detec...
Data
Neutralization analysis of signature amino acids in the MPER region. (A) Schematic of gp41 region indicates the position of mutated amino acids mutated. (B) Neutralization sensitivity of infant T/F viruses from 100997i and 102407i and their mutants to paired maternal plasma. ID50 of infant T/F variants (blue bars) and their point mutants (red bars)...
Article
Full-text available
Herpes simplex virus type 2 (HSV-2) is the causative pathogen of genital herpes and is closely associated with the occurrence of cervical cancer and human immunodeficiency virus (HIV) infection. The absence of an effective vaccine and the emergence of drug resistance to commonly used nucleoside analogs emphasize the urgent need for alternative anti...
Article
Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination. The development of a novel pertussis vaccine, especially an intranasal (i.n.) vaccine is undoubtedly necessary, and mucosal adjuvants have been explored to enhance the immune response. In the present study, bacterium-like particl...
Article
Full-text available
Background Mutations rapidly accumulate in the HIV-1 genome after infection. Some of those mutations are selected by host immune responses and often cause viral fitness losses. This study is to investigate whether strongly selected mutations that are not associated with immune responses result in fitness losses. Results Strongly selected mutations...
Article
Objective: Non-human primates (NHPs) are the only animal model that can be used to evaluate protection efficacy of HIV-1 Env vaccines. However, whether broadly neutralizing antibodies (bnAbs) can be elicited in NHPs infected with simian/human immunodeficiency virus (SHIV) has not been fully understood. The objective of this study is to investigate...
Article
Full-text available
A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced...
Article
Superinfection is frequently detected among individuals infected by human immunodeficiency virus type I (HIV-1). Superinfection occurs at similar frequencies at acute and chronic infection stages but less frequently than primary infection. This observation indicates that the immune responses elicited by natural HIV-1 infection may play a role in cu...
Preprint
Despite extensive genetic diversity of HIV-1 in chronic infection, infant HIV-1 infection involves selective transmission of a single or few maternal virus variants. These transmitted/founder (T/F) variants are of particular interest, as a maternal or infant HIV vaccine should raise envelope (Env)-specific IgG responses capable of blocking this gro...
Article
Full-text available
In order to inform the rational design of HIV-1 preventive and cure interventions it is critical to understand the events occurring during acute HIV-1 infection (AHI). Using viral deep sequencing on six participants from the early capture acute infection RV217 cohort, we have studied HIV-1 evolution in plasma collected twice weekly during the first...
Data
Viral dynamics in the HIV-1 subgenomic areas encoding for a) p2, b) vif, c) vpr, and d) env as revealed by TDS in participant 40061. CTL epitopes are shaded and variants derived from the major (Mj) and minor (mn) T/F viruses are indicated. (PDF)
Data
Phylogenetic analysis of within-patient and between-patient genetic diversity in Thailand and East Africa. In order to assess if cognate T/F viruses in the current RV217 data set were acquired from the same or different donors, we downloaded from the Los Alamos HIV Database all available env nucleotide sequences from Thailand (n = 3446) and East Af...
Data
Viral dynamics in the HIV-1 subgenomic areas encoding for a) pol, b) V5 loop in gp120, and c) nef as revealed by TDS in participant 40100. The variants sequences, their frequency, and their contribution to the total viral load (gray area) are shown. (PDF)
Data
Viral dynamics in the HIV-1 subgenomic areas encoding for a) p7, b) C3V4, and c) gp41 as revealed by TDS in participant 40436. Variants derived from the major (Mj) and minor (mn) T/F viruses are indicated. (PDF)
Data
Viral dynamics in the HIV-1 subgenomic areas encoding for a) p17, b) RNase, c) Int, and d) env/rev as revealed by TDS in participant 40265. Variants derived from the major (Mj) and minor (mn) T/F viruses are indicated. (PDF)
Data
Viral dynamics in the HIV-1 subgenomic area encoding for env/rev as revealed by TDS in participant 40265. Lineages derived from the major (Mj) and minor (mn) T/F viruses, as well as variants in the putative CTL epitopes in Rev and Env are indicated, following the nomenclature used in Fig 3 and S10 Fig. (PDF)