Research on Maternal Vaccination for HIV Prevention.

Despite increased uptake of antiretroviral therapy (ART) among pregnant people living with human immunodeficiency virus (HIV), vertical transmission remains the most important route of pediatric HIV acquisition. The numbers of HIV acquisitions in infancy have remained alarmingly stagnant in recent years. It is evident that additional strategies that can synergize with ART will be required to end the pediatric HIV epidemic. In this review, we discuss the potential for immune-based interventions that can be administered in conjunction with current ART-based strategies to the birthing parent for prevention of vertical transmission of HIV-1, and the potential challenges associated with each approach.

Passive immunoprophylaxis with Ccombodies against Vibrio parahaemolyticus in Pacific white shrimp (Penaeus vannamei).

The Vibrio parahaemolyticus strain causing acute hepatopancreatic necrosis disease (AHPND) in shrimp secretes toxins A and B (PirAVp/PirBVp). These toxins have been implicated in pathogenesis and are targets for developing anti-AHPND therapeutics or prophylactics that include passive immunization. We have previously reported that Ccombodies (recombinant hagfish variable lymphocyte receptor B antibodies; VLRB) targeting PirBVp conferred protection against V. parahaemolyticus in shrimp when administered as a feed supplement. In this study, we screened a phage-displayed library of engineered VLRBs for PirAVp-targeting Ccombodies that were mass-produced in a bacterial expression system. We then introduced these Ccombodies into the diet of Pacific white shrimp (Penaeus vannamei) over a seven-day period. Subsequently, the shrimp were exposed to a challenge with V. parahaemolyticus. Mortality rates were then observed and recorded over the following seven days. Administering shrimp feed supplemented with Ccombodies at a high dose (100 mg per 100 g feed) reduced mortality in recipient animals (2.96-5.19 %) statistically similar to mock-challenged control (1.48 %), but significantly different from the Ccombody-deficient control (74.81 %). This suggests that the Ccombodies provided strong protection against the bacterium. Feeding shrimp with a median dose (10 mg/100 g feed) gave statistically comparable low mortality (5.93-6.67 %) as the high dose. Reducing the Ccombody dose to 1 mg/100 g feed showed variable effects. Ccombody A2 showed mortality (11.85 %) significantly lower than that of the Ccombody-deficient group (74.81 %), suggesting that it can effectively protect against the bacterial challenge at a low dose. Our results demonstrate the ability of the phage-displayed VLRB library to generate antigen-specific Ccombodies rapidly and simply, with the expression of high protein levels in bacteria. The protective effect provided by these Ccombodies aligns with our earlier results, strongly supporting the use of VLRB antibodies as a substitute for IgY in passive immunoprophylaxis against AHPND in shrimp.

Vaccines: Do they have a role in orthopedic trauma?

Although vaccines have been hailed as one of the greatest advances in medicine based on their unparalleled cost-effectiveness in eradicating life-threatening infectious diseases, their role in orthopedic trauma-related infections is unclear. This is largely because vaccines are primarily made against pathogens that cause communicable diseases rather than opportunistic infections secondary to trauma, and most successful vaccines are against viruses rather than biofilm forming bacteria. Nonetheless, the tremendous costs to patients and healthcare systems warrant orthopedic trauma vaccine research, which has been a focal topic in recent international consensus meetings on musculoskeletal infection. This subject was also covered at the 2023 Osteosynthesis and Trauma Care Foundation (OTCF) meeting in Rome, Italy, and the purpose of this supplement article is to (1) highlight the osteoimmunology, animal models, translational research and clinical pilots that were discussed, (2) the proposed future directions that could lead to diagnostics and prognostics that are critically needed for evidence-based decision making, and (3) vaccines and passive-immunization strategies that could potentially be utilized to treat patients with orthopedic infections.

Supplementation with avian-derived polyclonal antibodies against Methanobrevibacter gottschalkii and M. ruminantium decreases ex vivo methane production and modifies ruminal fermentation in Angus crossbred steers.

The study aimed to investigate the effect of supplementing polyclonal antibodies (PAP) of avian origin against the ruminal methanogens Methanobrevibacter gottschalkii Ho (PAP-Ho) and M. ruminantium M1 (PAP-M1) on ruminal fermentation profile and methane production in Angus crossbred cattle (13 steers and 1 heifer). The experiment was conducted using a randomized block design with a 3 × 2 + 1 factorial arrangement, replicated in 3 periods. The factors included proportions of PAP against Ho and M1 in the mixture (100:0, 50:50, and 0:100 Ho:M1) and level of each mixture (3- or 6-mL per d). Cattle in control treatment did not receive PAP supplementation. Ruminal fluid was collected from the animals on days 0, 14, and 21 of treatment to determine of ruminal fermentation profile and ex vivo methane production. There was no effect of level of inclusion on ex vivo methane production. Supplementation with PAP-M1, either alone or in combination with PAP-Ho, decreased ex vivo methane output compared to the control group. Furthermore, in vivo molar proportion of propionate tended to be greater with PAP-M1, alone or combined with PAP-Ho, when compared with the control group. The study concluded that polyclonal antibodies against ruminal methanogens have the potential to decrease enteric methane emissions in cattle. The research provided important insights into the potential use of PAP as a strategy for reducing greenhouse gas emissions from cattle. Further research is needed to confirm these findings and to determine the practicality and feasibility of using PAP.

Methane is produced by methanogens, a type of microorganism that inhabits environments with low or no oxygen, for instance, the rumen of cattle. Methane is a greenhouse gas, and its emission contributes to climate change. Antibodies are proteins produced by the immune system when foreign bodies, called antigens, enter the body. Antibodies bind antigens and inhibit their negative actions. This study aimed to determine if oral supplementation of cattle with antibodies produced against 2 species of ruminal methanogens can decrease methane emissions from cattle. Different mixtures and doses of the 2 antibodies were supplemented to Angus crossbred animals for 21 d. Ruminal fluid from each animal was collected and incubated for 48 h to determine methane production and concentration of fermentation metabolites. There was no difference between supplementing low or high levels of antibodies. Supplementation with antibodies can result in up to 13% lower methane emissions and, in addition, production of fermentation metabolites was also affected. In summary, even a low dose of antibodies against methanogens could potentially decrease methane emissions from cattle and could become a technology to mitigate the negative effects of methane on climate.

Dual neutralization of influenza virus hemagglutinin and neuraminidase by a bispecific antibody leads to improved antiviral activity.

Targeting multiple viral proteins is pivotal for sustained suppression of highly mutable viruses. In recent years, broadly neutralizing antibodies that target the influenza virus hemagglutinin and neuraminidase glycoproteins have been developed, and antibody monotherapy has been tested in preclinical and clinical studies to treat or prevent influenza virus infection. However, the impact of dual neutralization of the hemagglutinin and neuraminidase on the course of infection, as well as its therapeutic potential, has not been thoroughly tested. For this purpose, we generated a bispecific antibody that neutralizes both the hemagglutinin and the neuraminidase of influenza viruses. We demonstrated that this bispecific antibody has a dual-antiviral activity as it blocks infection and prevents the release of progeny viruses from the infected cells. We show that dual neutralization of the hemagglutinin and the neuraminidase by a bispecific antibody is advantageous over monoclonal antibody combination as it resulted an improved neutralization capacity and augmented the antibody effector functions. Notably, the bispecific antibody showed enhanced antiviral activity in influenza virus-infected mice, reduced mice mortality, and limited the virus mutation profile upon antibody administration. Thus, dual neutralization of the hemagglutinin and neuraminidase could be effective in controlling influenza virus infection.

Implementation of the first respiratory syncytial (RSV) immunization campaign with nirsevimab in an autonomous community in Spain.

Respiratory syncytial virus (RSV) is the main cause of low respiratory tract infections in infants under one year of age. In the 2023/2024 season, the monoclonal antibody nirsevimab was available to protect children from RSV, and Spain has become one of the first countries worldwide to implement this strategy. It is essential to evaluate the results of this first campaign and different characteristics of the immunized population in order to plan next campaigns, especially for countries that are going to include this immunization. Our coverage was high (91.5% for those born during the season and 88.3% globally). For those born during the season, only 4.9% preferred not to immunize at the maternity hospital, which meant an average delay of 27.45 days. We observed a lower coverage in the population of immigrant origin. There was a rapid pace of immunization, since for those born before the beginning of the campaign the mean to be immunized was 15.63 days, without differences between healthy and at-risk children. This allows immunization before the RSV season (90% of the catch-up children had been immunized on November 3). The average age at which all the immunized children have received nirsevimab was lower in healthy children compared to those with risk conditions (49.65 versus 232.85 days). For those born during the campaign, the average age was also lower in healthy children (3.14 versus 14.58 days). In conclusion, we consider that the implementation of the immunization strategy with nirsevimab in the Region of Murcia, Spain, has been a success.

Passive immunization of mice with IgY anti-H5N1 protects against experimental influenza virus infection and allows development of protective immunity.

Influenza virus contributes substantially to the global human and animal disease burden. To protect individuals against disease, strategies are needed to minimize the time an individual is at risk of developing disease symptoms. Passive immunization using avian IgY antibodies can protect individuals against a variety of pathogens, including influenza virus. Yet the effect of IgY administration on generation of protective immunity is largely unknown. To address the effect of passive immunization on the host immune response development, adult or aged, male and female C57BL/6NCrl mice received chicken IgY anti-H5N1, normal IgY or PBS intranasally four hours before, and 20 hours after intranasal infection with H1N1 influenza A virus (PR8). The mice receiving cross-reactive IgY anti-H5N1 were protected from disease and developed influenza virus-specific memory T cells similar to control-treated mice. When re-challenged with PR8 35 days post primary infection IgY anti-H5N1-treated mice were fully protected. Moreover, when challenged with heterologous H3N2 influenza A virus (X-31) or with PR8 three months post infection the mice were protected against severe disease and death, albeit a slight transient weight loss was noted. The results show that passive immunization with IgY anti-H5N1 is safe and protects mice against disease induced by influenza virus without inhibiting development of protective immunity after virus exposure. This indicate that passive immunization can be used as prophylactic therapy in combination with immunization to prevent disease.

Prophylactic antibodies inhibit spike-specific T and B cell responses after COVID-19 vaccination.

Active and passive immunization is used in high-risk patients to prevent severe courses of COVID-19, but the impact of prophylactic neutralizing antibodies on the immune reaction to the mRNA vaccines has remained enigmatic. Here we show that CD4 T and B cell responses to Spikevax booster immunization are suppressed by the therapeutic antibodies Casirivimab and Imdevimab. B cell and T cell responses were significantly induced in controls but not in antibody-treated patients. The data indicates that humoral immunity, i. e. high levels of antibodies, negatively impacts reactive immunity, resulting in blunted cellular responses upon boosting. This argues for temporal separation of vaccination efforts; with active vaccination preferably applied before prophylactic therapeutic antibody treatment.

Advances and challenges in the development of periodontitis vaccines: A comprehensive review.

Periodontitis is a prevalent polymicrobial disease. It damages soft tissues and alveolar bone, and causes a significant public-health burden. Development of an advanced therapeutic approach and exploration of vaccines against periodontitis hold promise as potential treatment avenues. Clinical trials for a periodontitis vaccine are lacking. Therefore, it is crucial to address the urgent need for developing strategies to implement vaccines at the primary level of prevention in public health. A deep understanding of the principles and mechanisms of action of vaccines plays a crucial role in the successful development of vaccines and their clinical translation. This review aims to provide a comprehensive summary of potential directions for the development of highly efficacious periodontitis vaccines. In addition, we address the limitations of these endeavors and explore future possibilities for the development of an efficacious vaccine against periodontitis.

Effectiveness of nirsevimab introduction against respiratory syncytial virus in the Valencian Community: A preliminary assessment.

Respiratory syncytial virus (RSV) represents a high burden of disease in children and the primary cause of hospitalization, especially in children under 1 year old. In the Valencian Community (Spain), nirsevimab, a long-acting monoclonal antibody, was introduced for the RSV 2023-2024 season as a universal pre-exposure prophylaxis for high-risk children and those under 6 months old. This study examines its impact, coverage, and effectiveness. The campaign achieved 88.5 % coverage and 73.7 % of effectiveness. Analysis of over 27,000 susceptible children (over 24,000 immunized), showed that those immunized exhibited a threefold reduction in RSV incidence compared to non-immunized ones. To prevent one case, the number needed to immunize (NNI) was 63. Hospitalizations due to acute respiratory infections were almost two times lower in immunized children compared to non-immunized ones (0.9 % vs 1.6 %, respectively). These first results showcase the preliminary positive impact of this public health intervention.

Development of fentanyl-specific monoclonal antibody (mAb) to antagonize the pharmacological effects of fentanyl.

Fentanyl, a critical component of opioid analgesics, poses a severe threat to public health, exacerbating the drug problem due to its potential fatality. Herein, we present two novel haptens designed with different attachment sites conjugated to keyhole limpet hemocyanin (KLH), aiming to develop an efficacious vaccine against fentanyl. KLH-Fent-1 demonstrated superior performance over KLH-Fent-2 in antibody titer, blood-brain distribution, and antinociceptive tests. Consequently, we immunized mice with KLH-Fent-1 to generate fentanyl-specific monoclonal antibodies (mAbs) using the hybridoma technique to compensate for the defects of active immunization in the treatment of opioid overdose and addiction. The mAb produced by hybridoma 9D5 exhibited the ability to recognize fentanyl and its analogs with a binding affinity of 10-10 M. Subsequently, we developed a human IgG1 chimeric mAb to improve the degree of humanization. Pre-treatment with murine and chimeric mAb significantly reduced the analgesic effect of fentanyl and altered its blood-brain biodistribution in vivo. Furthermore, in a mouse model of fentanyl-induced respiratory depression, the chimeric mAb effectively reversed respiratory depression promptly and maintained a certain level during the week. The development of high-affinity chimeric mAb gives support to combat the challenges of fentanyl misuse and its detrimental consequences. In conclusion, mAb passive immunization represents a viable strategy for addressing fentanyl addiction and overdose.

The fentanyl-specific antibody FenAb024 can shield against carfentanil effects.

The surge in opioid-related deaths, driven predominantly by fentanyl and its synthetic derivatives, has become a critical public health concern, which is particularly evident in the United States. While the situation is less severe in Europe, the European Monitoring Centre for Drugs and Drug Addiction reports a rise in drug overdose deaths, with emerging concerns about the impact of fentanyl-related molecules. Synthetic opioids, initially designed for medical use, have infiltrated illicit markets due to their low production costs and high potency, with carfentanil posing additional threats, including potential chemical weaponization. Existing overdose mitigation heavily relies on naloxone, requiring timely intervention and caregiver presence, while therapeutic prevention strategies face many access challenges. To provide an additional treatment option, we propose the use of a fentanyl-specific monoclonal antibody (mAb), as a non-opioid method of prophylaxis against fentanyl and carfentanil. This mAb shows protection from opioid effects in a pre-clinical murine model. mAbs could emerge as a versatile countermeasure in civilian and biodefense settings, offering a novel approach to combat opioid-associated mortality.

New and Emerging Passive Immunization Strategies for the Prevention of RSV Infection During Infancy.

To date, safe and effective strategies to prevent medically attended respiratory syncytial virus (RSV) illness across the infant population have been limited to passive immunoprophylaxis for those at highest risk. While active vaccination strategies are finally available to protect adults 60 years and older from serious RSV infection, safe and effective vaccines for use in children have yet to emerge. In contrast, passive immunization strategies designed to protect all infants against RSV has finally met with success, with 2 new strategies approved by the US Food and Drug Administration during the second half of 2023. The first RSV passive immunization strategy to gain licensure for use in all infants is an extended half-life monoclonal antibody directed against an antigenic binding site on the RSV-F prefusion protein, a conformation not known to exist until 2013. The second novel passive immunization strategy approved during 2023 that has the potential to protect much of the infant population from RSV during young infancy centers on boosting preexisting RSV immunity during pregnancy using a prefusion RSV-F vaccine. The resulting boosted humoral immune response to RSV in the mother becomes part of the transplacental antibody endowment that is actively transported across the placenta to provide protection to those babies born at or near term. This review describes how and why these advances came to fruition seemingly "all at once" and provides insight into other passive immunization approaches that remain under development.

Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.

Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Reducing huntingtin by immunotherapy delays disease progression in a mouse model of Huntington disease.

In Huntington disease (HD), the mutant huntingtin (mtHTT) protein is the principal cause of pathological changes that initiate primarily along the cortico-striatal axis. mtHTT is ubiquitously expressed and there is, accordingly, growing recognition that HD is a systemic disorder with functional interplay between the brain and the periphery. We have developed a monoclonal antibody, C6-17, targeting an exposed region of HTT near the aa586 Caspase 6 cleavage site. As recently published, mAB C6-17 can block cell-to-cell propagation of mtHTT in vitro. In order to reduce the burden of the mutant protein in vivo, we queried whether extracellular mtHTT could be therapeutically targeted in YAC128 HD mice. In a series of proof of concept experiments, we found that systemic mAB C6-17 treatment resulted in the distribution of the mAB C6-17 to peripheral and CNS tissues and led to the reduction of HTT protein levels. Compared to CTRL mAB or vehicle treated mice, the mAB C6-17 treated YAC128 animals showed improved body weight and motor behaviors, a delayed progression in motor deficits and reduced striatal EM48 immunoreactivity. These results provide the first proof of concept for the feasibility and therapeutic efficacy of an antibody-based anti-HTT passive immunization approach and suggest this modality as a potential new HD treatment strategy.

[The burden of COVID-19 in a heterogeneous population of immunocompromised patients - realities of the postpandemic].

On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.

Cell-based passive immunization for protection against SARS-CoV-2 infection.

BACKGROUND: Immunologically impaired individuals respond poorly to vaccines, highlighting the need for additional strategies to protect these vulnerable populations from COVID-19. While monoclonal antibodies (mAbs) have emerged as promising tools to manage infectious diseases, the transient lifespan of neutralizing mAbs in patients limits their ability to confer lasting, passive prophylaxis from SARS-CoV-2. Here, we attempted to solve this problem by combining cell and mAb engineering in a way that provides durable immune protection against viral infection using safe and universal cell therapy. METHODS: Mouse embryonic stem cells equipped with our FailSafe™ and induced allogeneic cell tolerance technologies were engineered to express factors that potently neutralize SARS-CoV-2, which we call 'neutralizing biologics' (nBios). We subcutaneously transplanted the transgenic cells into mice and longitudinally assessed the ability of the cells to deliver nBios into circulation. To do so, we quantified plasma nBio concentrations and SARS-CoV-2 neutralizing activity over time in transplant recipients. Finally, using similar cell engineering strategies, we genetically modified FailSafe™ human-induced pluripotent stem cells to express SARS-CoV-2 nBios. RESULTS: Transgenic mouse embryonic stem cells engineered for safety and allogeneic-acceptance can secrete functional and potent SARS-CoV-2 nBios. As a dormant, subcutaneous tissue, the transgenic cells and their differentiated derivatives long-term deliver a supply of protective nBio titers in vivo. Moving toward clinical relevance, we also show that human-induced pluripotent stem cells, similarly engineered for safety, can secrete highly potent nBios. CONCLUSIONS: Together, these findings show the promise and potential of using 'off-the-shelf' cell products that secrete neutralizing antibodies for sustained protective immunity against current and future viral pathogens of public health significance.

Polyvalent passive vaccine candidates from egg yolk antibodies (IgY) of important outer membrane proteins (PF1380 and ExbB) of Pseudomonas fluorescens in fish.

Polyvalent antibodies can resist multiple bacterial species, and immunoglobulin Y (IgY) antibody can be economically prepared in large quantities from egg yolk; further, IgY polyvalent antibodies have application value in aquaculture. The outer membrane proteins (OMPs) PF1380 and ExbB of Pseudomonas fluorescens were expressed and purified, and the corresponding IgY antibodies were prepared. PF1380, ExbB, and the corresponding IgY antibodies could activate the innate immune responses of chicken and Carassius auratus. The passive immunization to C. auratus showed that the IgY antibodies of PF1380 and ExbB had an immune protection rate, down-regulated the expression of antioxidant-related factors (MDA, SOD, GSH-Px, and CAT) to reduce the antioxidant reaction, down-regulated the expression of inflammation-related genes (IL-6, IL-8, TNF-α, and IL-1ß) to reduce the inflammatory reaction, maintained the integrity of visceral tissue structure, and reduced apoptosis and damage of tissue cells in relation to P. fluorescens and Aeromonas hydrophila infections. Thus, the IgY antibodies of PF1380 and ExbB could be considered as passive polyvalent vaccine candidates in aquaculture.

Recent Advancements in AAV-Vectored Immunoprophylaxis in the Nonhuman Primate Model.

Monoclonal antibodies (mAbs) are important treatment modalities for preventing and treating infectious diseases, especially for those lacking prophylactic vaccines or effective therapies. Recent advances in mAb gene cloning from naturally infected or immunized individuals has led to the development of highly potent human mAbs against a wide range of human and animal pathogens. While effective, the serum half-lives of mAbs are quite variable, with single administrations usually resulting in short-term protection, requiring repeated doses to maintain therapeutic concentrations for extended periods of time. Moreover, due to their limited time in circulation, mAb therapies are rarely given prophylactically; instead, they are generally administered therapeutically after the onset of symptoms, thus preventing mortality, but not morbidity. Adeno-associated virus (AAV) vectors have an established record of high-efficiency in vivo gene transfer in a variety of animal models and humans. When delivered to post-mitotic tissues such as skeletal muscle, brain, and heart, or to organs in which cells turn over slowly, such as the liver and lungs, AAV vector genomes assume the form of episomal concatemers that direct transgene expression, often for the lifetime of the cell. Based on these attributes, many research groups have explored AAV-vectored delivery of highly potent mAb genes as a strategy to enable long-term expression of therapeutic mAbs directly in vivo following intramuscular or intranasal administration. However, clinical trials in humans and studies in nonhuman primates (NHPs) indicate that while AAVs are a powerful and promising platform for vectored immunoprophylaxis (VIP), further optimization is needed to decrease anti-drug antibody (ADA) and anti-capsid antibody responses, ultimately leading to increased serum transgene expression levels and improved therapeutic efficacy. The following review will summarize the current landscape of AAV VIP in NHP models, with an emphasis on vector and transgene design as well as general delivery system optimization. In addition, major obstacles to AAV VIP, along with implications for clinical translation, will be discussed.

Broadly neutralizing antibodies consistently trap HIV-1 in fresh cervicovaginal mucus from select individuals.

In addition to direct neutralization and other classical effector functions, IgG possesses a little recognized and thus under-utilized effector function at mucosal surfaces: Fc-mucin bonds enable IgG to trap viruses in mucus. Due to the paucity of envelope glycoproteins that limits the number of IgG that can bind HIV, it remains poorly understood whether IgG-mucin interactions can effectively immobilize HIV in human cervicovaginal mucus (CVM). Here, we obtained 54 fresh, undiluted CVM specimens from 17 different women, and employed high-resolution multiple particle tracking to quantify the mobility of fluorescent HIV virus-like-particles in CVM treated with various HIV-specific IgG. We observed consistent and effective trapping of HIV by broadly neutralizing antibodies (VRC01, PGT121, and 2F5) in a subset of women. While trapping efficacy was not affected by the menstrual cycle, it was positively correlated with appreciable L. Crispatus populations in the microbiome, and negatively correlated with appreciable L. Iners or G. Vaginalis populations. Our work demonstrates for the first time that IgG-mucin crosslinking is capable of reinforcing the mucosal barrier against HIV, and motivates further investigation of passive immunization against vaginal transmission of STIs. STATEMENT OF SIGNIFICANCE: HIV transmission in women primarily occurs vaginally, yet the 3-way interactions between mucins and HIV virions mediated by HIV-binding antibodies in cervicovaginal mucus (CVM) is not well understood. While IgG-Fc possess weak affinity to mucins that trap virus/IgG complexes in mucus, the effectiveness against HIV remains unclear, due to the low number of virion-bound IgG. Here, we discovered that IgG can trap HIV consistently in CVM from select individuals regardless of their birth control status or menstrual cycle phase. IgG-mediated trapping of HIV was moderately associated with microbiome composition. These results suggest that IgG-mucin interactions could potentially reduce HIV transmission and highlight the importance of mucosal secretions in antibody-mediated prevention of HIV and other sexually transmitted infections.