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Synthetic cannabinoids (SCs) constitute a significant portion of psychoactive substances forming a major public health risk. Due to the wide variety of SCs, broadly neutralizing antibodies generated by active immunization present an intriguing pathway to combat cannabinoid use disorder. Here, we probed hapten design for antibody affinity and cross reactivity against two classes of SCs. Of the 10 haptens screened, 3 vaccine groups revealed submicromolar IC50, each targeting 5-6 compounds in our panel of 22 drugs. Moreover, SCs were successfully sequestered when administered by vaping or intraperitoneal injection, which was confirmed within animal models by observing locomotion, body temperature, and pharmacokinetics. We also discovered synergistic effects to simultaneously blunt two drug classes through an admixture vaccine approach. Collectively, our study provides a comprehensive foundation for the development of vaccines against SCs.

Resumen El tétanos generalizado es una enfermedad infecciosa altamente mortal sin intervenciones médicas y en nuestro tiempo, prevenible mediante inmunización activa. Se presenta el caso de un preescolar de 4 años quien sufre herida cortante en la palma de la mano izquierda y quien se presenta 4 días más tarde con datos clínicos de tétanos generalizado. Fue intubado y admitido a la terapia intensiva del Hospital del Niño Dr. José Renán Esquivel. Su hospitalización se vio caracterizada por neumonía nosocomial, una lesión anfractuosa lingual e inestabilidad autonómica. Además de la antibioticoterapia con metronidazol y la aplicación de inmunoglobulina antitetánica, precisó apoyo hemodinámico con dobutamina y norepinefrina. Para lograr un completo control de las crisis de hipertonía, se ofreció manejo con infusión de midazolam, levetiracetam, clobazam, baclofeno y toxina botulínica. Palabras clave: tétanos generalizado, inmunización, inestabilidad autonómica, opistótonos, trismos.

PURPOSE OF REVIEW Simian--human immunodeficiency viruses (SHIVs), chimeric viruses that encode HIV-1 Env within an SIV backbone, are key reagents for nonhuman primate studies of antibody-based vaccines, broadly neutralizing antibodies (bnAbs), and other Env-targeting reagents. Here, we discuss the provenance and characteristics of currently relevant SHIVs, novel technical advances, recent discoveries enabled by SHIV challenge studies, and the continued development of SHIVs for persistence and cure experiments. RECENT FINDINGS SHIV SF162P3, SHIV AD8EO, and transmitter/founder SHIVs with Env375 mutations are now common reagents in nonhuman primate studies, with increased use and validation establishing their properties and potential applications. Genetic barcoding of SIV and SHIV, which allows tracing of individual lineages and elucidation of viral kinetics from transmission through latency has expanded the experimental capacity of SHIV models. SHIV challenge studies have determined the neutralizing antibody titers that correlate with protection for passive and active immunization and enabled complementary human and nonhuman primate studies of vaccine development. SHIV models of latency continue to evolve, aided by descriptions of SHIV persistence on ART and the proviral landscape. SUMMARY Recent advances and more thorough characterization of SHIVs allow for expanded applications and greater confidence in experimental results.

Advanced age is associated with an increase in morbidity and mortality from influenza. Immunization is the best option to protect individuals against influenza and its complications. Older people are less likely than their younger counterparts to mount an appropriate immune response to influenza vaccines. The adjuvanted inactivated influenza vaccine quadrivalent (aIIV4) is designed to elicit a more robust immune response in older people compared with traditional inactivated influenza vaccines. The aIIV4 is indicated for active immunization against influenza caused by influenza virus subtypes A and types B contained in the vaccine and is licensed by the Food and Drug Administration for use in persons 65 years of age and older. The aIIV4 should be administered by intramuscular injection. Like other influenza vaccines, aIIV4 carries a warning regarding the occurrence of Guillain-Barré syndrome. The most common adverse reactions associated with aIIV4 are injection site pain, fatigue, headache, arthralgia, and myalgia.

The best way to prevent a highly contagious infection such as measles is active immunization with a suitable vaccine. Unfortunately, in the last 10 years in EU there has been a decrease in vaccinat...

The anaerobic pathogen Clostridium perfringens is the most potent cause of intestinal diseases, such as enterotoxemia, hemorrhagic enteritis, and lamb dysentery, in sheep. Three toxinotypes (B, C, and D) are usually the cause of these diseases and are mainly mediated via three important exotoxins: alpha toxin (CPA), beta toxin (CPB), and epsilon toxin (ETX). We have designed a chimeric protein, rCpa-b-x, that contains the C-terminal binding region of CPA, partial sequence of CPB, and ETX (Cpa247-370, Cpb108-305, and EtxH118P, respectively) according to the principle of structural vaccinology. The rCpa-b-x protein was then expressed by pHT43 plasmid in vivo using Bacillus subtilis as a delivery vector (Bs-pHT43-Cpa-b-x). The immunological activity of the rCpa-b-x protein was verified by western blot and its immunological efficacy was evaluated in a murine model. Oral administration with a recombinant agent caused local mucosal and systemic immune responses, and serum lgG and intestinal mucosal secretory IgA (sIgA) antibody titers were significantly increased. Levels of IL-2, IL-4, and IFN-γ were significantly higher in lymphocytes isolated from the Bs-pHT43-Cpa-b-x group compared with levels from the control groups. The percentages of CD4+ and CD8+ T lymphocytes in the Bs-pHT43-Cpa-b-x and inactivated vaccine (IV) groups were in the normal range. Mice of vaccine groups and control groups were challenged with 1x LD100 unit filtrate containing alpha, beta, and epsilon toxins. Mice in the Bs-pHT43-Cpa-b-x group were found to have lower rates of morbidity. The active immunization of mice with Bs-pHT43-Cpa-b-x still maintained 85% to 90% survival at the end of the 10-day observation period, whereas mice of control groups died within two to five days. The results of this study demonstrate the effectiveness of Bs-pHT43-Cpa-b-x in preventing C. perfringens infection in mice, and that Bs-pHT43-Cpa-b-x could be considered a potential vaccine against C. perfringens.

Background Acinetobacter baumannii, a nosocomial pathogen, is considered as a common cause of hospital and community-acquired infections. Emerging multidrug-resistance in this pathogen followed by subsequent problems in treatment has been increasing to alarming levels that warrant investigation of new therapeutic approaches. One strategy to reduce antibiotic resistance is to use of vaccines. Although there is no vaccine currently in development for this pathogen, different attempts have been made to develop one. Methods In this study, we used two different recombinant pilus proteins (CsuA/B and FimA) either singly or in combination to evaluate protective efficacy against A. baumannii in lethal and sub-lethal murine sepsis models. Findings Active immunization with recombinant proteins in combination elicited high levels of IgG antibody after the first immunization and provided 62% (five of eight mice; p Interpretation Our results showed that pilus proteins in combination as a single immunogen could potentially impart protection against A. baumannii. Funding Shahed University.

The objective of this review article was to discuss the interaction between virus effectiveness and host immune system challenges on the innate and adaptive on how the immune system able to defend against COVID-19 viral infections. Genetically, the COVID-19 is a virus that has genetic material coated by lipid with a crown of protein. The virus that causes COVID-19 is called severe acute respiratory syndrome coronavirus two (SARS-COV-2) and was first detected in humans last December 2019. Primarily, the COVID-19 virus spreads with droplets of saliva or nose discharge when an infected person sneezes or coughs. Most people with a healthy immune system those infected with the COVID-19 virus showed mild to moderate respiratory illness and recovered without needing special treatment. The aged people those had medical problems such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer are most likely to develop serious illness. In-conclusion: Little is known about viral clearance, but regulation innate immune response associated with development of adaptive immunity neutralizing antibodies, memory T and B lymphocytes in convalescent patients raises hope for active immunization.

Beef cattle farming is a highly representative activity for the GDP of Brazil, rendering the country an important producer of beef. For Brazil to maintain this prominent position, sanitary management actions must be carried out, such as the control of reproductive diseases. This study examines the effectiveness of vaccination against reproductive diseases in bovine females. Data from 8752 Zebu cows on the status of vaccination against reproductive diseases, body condition score (BCS) and the subsequent result of pregnancy diagnosis were evaluated. With regard to BCS, primiparous was the category that most demonstrated the effect of body condition on pregnancy rate, with BCS 3.5 cows having a 30% higher rate than the animals with BCS 2. In the group of nulliparous cows, those with BCS 3.5 had a pregnancy rate of 58% vs. 46% in BCS 3 cows. The induced nulliparae with BCS 3.5 had a 9% higher pregnancy rate than those with BCS 3. Multiparous cows also had a 9% higher rate when their BCS was 3.5 as compared with BCS 2. Among the evaluated dams, 46.5% were vaccinated against IBR, BVD and leptospirosis. Of these, the primiparae showed a 21% increase in conception as compared with the non-vaccinated group; multiparae, 10%; nulliparae, 5.9%; and induced nulliparae, 7.8%. In conclusion, BCS directly influences the reproductive efficiency of bovine females, and the use of vaccination against reproductive diseases can be recommended. However, this indication must be based on epidemiological and animal-performance data of each farm.

The aim of this study was to investigate the effects of active immunization against recombinant Anti-Müllerian hormone (AMH) protein on the ovarian follicular development, egg production, and molecular regulatory mechanisms in broody-prone Zhedong White geese. For this, a recombinant goose AMH protein was expressed using a prokaryotic expression system. Fifty incubating geese from the same genetic background were selected and equally divided into two groups. The immunization group was actively immunized against the recombinant goose AMH protein, whereas the control group was immunized against bovine serum albumin (BSA). Immunization against AMH accelerated ovarian follicular development and increased clutch sizes by one to two eggs in two consecutive laying-incubation cycles. Furthermore, immunization against AMH upregulated the mRNA transcription levels of the FSH-beta gene in the pituitary gland, and FSHR, 3beta-HSD, and Smad4 genes in the granulosa layer of pre-ovulatory follicles; however, immunization downregulated the expression of the OCLN gene in the granulosa layer of pre-ovulatory follicles, and Smad5 and Smad9 genes in the granulosa layer of SYFs. These results suggest that AMH might hinder ovarian follicular development by decreasing both pituitary FSH secretion as well as ovarian follicular sensitivity to FSH. The latter molecular mechanism could be fulfilled by regulating Smad5 or Smad9 signals in SYFs, as well as the FSHR and Smad4 signals that affect progesterone synthesis and yolk deposition in the pre-ovulatory follicles.

Background Fibroblast growth factor (FGF)-2 is overexpressed in various tumor tissues. It affects tumor cell proliferation, invasion and survival, promotes tumor angiogenesis and is tightly involved in the development of systemic and local immunosuppressive tumor mechanisms. Purpose This study aimed to develop an effective vaccine against FGF-2 and to investigate the effects of anti-FGF-2 immunization on tumor growth and antitumor immune responses. Methods A set of thirteen synthesized overlapping peptides covering all possible linear B-cell epitopes of murine FGF-2 and a recombinant FGF-2 protein were conjugated to virus-like particles (VLPs) of recombinant hepatitis B core antigen (HBcAg). The VLPs were immunized through a preventive or therapeutic strategy in a TC-1 or 4T1 grafted tumor model. Results Immunization with FGF-2 peptides or full-length protein-coupled VLPs produced FGF-2-specific antibodies with a high titer. Peptide 12, which is located in the heparin-binding site of FGF-2, or protein-conjugated VLPs presented the most significant effects on the suppression of TC-1 tumor growth. The levels of IFN-γ-expressing splenocytes and serum IFN-γ were significantly elevated; further, the immune effector cells CD8+ IFN-γ+ cytotoxic T lymphocytes (CTLs) and CD4+ IFN-γ+ Th1 cells were significantly increased, whereas the immunosuppressive cells CD4+ CD25+ FOXP3+ Treg cells and Gr-1+ CD11b+ myeloid-derived suppressor cells (MDSCs) were decreased in the immunized mice. In addition, VLP immunization significantly suppressed tumor vascularization and promoted tumor cell apoptosis. In mice bearing 4T1 breast tumor, preventive immunization with FGF-2-conjugated VLPs suppressed tumor growth and lung metastasis, and increased effector cell responses. Conclusion Active immunization against FGF-2 is a new possible strategy for tumor immunotherapy.

Chronic ethanol consumption in high doses is associated with constitutively elevated activity of the serum alcohol dehydrogenase I (ADH I) isoform, which demonstrates a high affinity not only for ethanol but also for a number of bioamine metabolites. Such excessive ADH activity is probably associated with disruptions in the metabolism of neurotransmitters (dopamine, serotonin, and norepinephrine) and subsequent long-term changes in the activity of their receptors. Ultimately, a stable depressive-like condition contributes to the development of patients' craving for ethanol intake, frequent disruptions during therapy, and low efficacy of treatment. We applied active immunization against ADH to investigate its efficacy in the reduction of excessive serum ADH activity and regulation of ethanol consumption by chronically ethanol-fed Wistar rats (15% ethanol, 4 months, free-choice method), and we analyzed its ability to influence the levels of bioamines in the brain. Immunization (2 injections, 2-week intervals) was performed using a combination of recombinant horse ADH isozyme as an antigen and 2% aluminum hydroxide-based adjuvant. The efficacy of immunization was demonstrated by the production of high titers of ADH-specific antibodies, which was consistent with the significantly reduced ADH activity in the serum of chronically ethanol-fed rats. On the 26th day after the first vaccine injection, we registered significantly lower levels of alcohol consumption compared to ethanol-fed control animals, and the difference reached 16% on the 49th day of the experiment. These observations were accompanied by data that showed reduced levels of ethanol preference in immunized rats. Chronic alcohol drinking led to a decrease in dopamine and DOPAL (a direct dopamine metabolite and a high-affinity ADH substrate) levels in the striatum,while immunization neutralized this effect. Additionally, we observed that inhibition of serum ADH activity caused a decrease in peak dopamine levels during acute alcohol intake in chronically ethanol-fed rats during ethanol withdrawal that was associated with reduced tyrosine hydroxylase activity in the striatum. The obtained data suggest a significant contribution of ADH to the changes in neurotransmitter systems during chronic alcohol consumption and make available new prospects for developing innovative strategies for treatment of excessive alcohol intake.

Inhalation of ricin toxin (RT), a Category B biothreat agent, provokes an acute respiratory distress syndrome marked by pro-inflammatory cytokine and chemokine production, neutrophilic exudate, and pulmonary edema. The severity of RT exposure is attributed to the tropism of the toxin’s B subunit (RTB) for alveolar macrophages and airway epithelial cells, coupled with the extraordinarily potent ribosome-inactivating properties of the toxin’s enzymatic subunit (RTA). While there are currently no vaccines or treatments approved to prevent RT intoxication, we recently described a humanized anti-RTA IgG1 MAb, huPB10, that was able to rescue non-human primates (NHPs) from lethal dose RT aerosol challenge if administered by intravenous (IV) infusion within hours of toxin exposure. We have now engineered an extended serum half-life variant of that MAb, huPB10-LS, and evaluated it as a pre-exposure prophylactic. Five Rhesus macaques that received a single intravenous infusion (25 mg/kg) of huPB10-LS survived a lethal dose aerosol RT challenge 28 days later, whereas three control animals succumbed to RT intoxication within 48 h. The huPB10-LS treated animals remained clinically normal in the hours and days following toxin insult, suggesting that pre-existing antibody levels were sufficient to neutralize RT locally. Moreover, pro-inflammatory markers in sera and BAL fluids collected 24 h following RT challenge were significantly dampened in huPB10-LS treated animals, as compared to controls. Finally, we found that all five surviving animals, within days after RT exposure, had anti-RT serum IgG titers against epitopes other than huPB10-LS, indicative of active immunization by residual RT and/or RT-immune complexes.

Active and passive anti-Aβ immunotherapies have successfully been used for the prevention and treatment of Alzheimer's disease animal models. However, clinical use of these immunotherapies is not effective, because the vaccination is administered too late. At 1 month of age, 100 μL of Aβ3-10-KLH peptide (vaccine, 2 μg/μL) was subcutaneously injected into the neck of an amyloid precursor protein/presenilin-1/tau transgenic (3×Tg-AD) mouse model. Aβ3-10-KLH peptide was re-injected at 1.5, 2.5, 3.5, 4.5, 5.5, and 6.5 months of age. Serum levels of Aβ antibody were detected by enzyme-linked immunosorbent assay, while spatial learning and memory ability were evaluated by Morris water maze. Immunohistochemistry was used to detect total tau with HT7 and phosphorylated tau with AT8 (phosphorylation sites Ser202 and Thr205) and AT180 (phosphorylation site Thr231) antibodies in the hippocampus. In addition, western blot analysis was used to quantify AT8 and AT180 expression in the hippocampus. The results showed that after vaccine injection, mice produced high levels of Aβ antibody, cognitive function was significantly improved, and total tau and phosphorylated tau levels were significantly reduced. These findings suggest that early active immunization with Aβ3-10-KLH vaccine can greatly reduce tau phosphorylation, thereby mitigating the cognitive decline of 3×Tg-AD mice. This study was approved by the Animal Ethics Committee of China Medical University, China (approval No. 103-316) on April 2, 2016.

A phase 2 clinical trial of active immunization against a pathological form of the tau protein provides evidence for feasibility of this approach. Although active treatment did not show benefits on clinical outcome measures, analyses of fluid biomarkers and of a subset of patients with predicted pathology provide hints of efficacy.

This study was conducted to investigate the potential effects of active immunization against recombinant-derived goose inhibin-α (INH-α), anti-Müllerian hormone (AMH), and prolactin (PRL) fusion protein on broodiness onset and egg production in geese. The purified fusion proteins (INH-α, AMH, and PRL) were prepared using a prokaryotic expression system. Female Zhedong geese (10 mo old) were randomly assigned to one of 4 treatments and raised in separate pens. The geese were actively immunized with the recombinant goose INH-α, AMH, or PRL, respectively, and phosphate-buffered saline as control. The results showed the corresponding antibodies were produced when the geese were immune INH-α, AMH-, and PRL-recombinant proteins. The significantly higher luteinizing hormone contents were observed in the INH-α, AMH, and PRL recombinant protein-immunized geese, while the lower AMH hormone content only in PRL-immunized birds. AMH recombinant protein immunized geese had more large yellow follicles of ovary, while the INHα-treated birds with more other follicles compared with control geese. In addition, the geese receiving INH-α recombinant protein, the broodiness onset was about 6 d, which significantly shorter than did PBS immunization (16 d). The INHα- and PRL-immunization also resulted in 12.5 and 8.5 d shorter broody duration intervals compared to the control birds. Moreover, the lower new broodiness rate was observed in three recombinant proteins treated birds. Finally, the PRL recombinant protein-immunization resulted in an average increase of 1.34 eggs during a 40-d observation. Collectively, the data demonstrated that active immunization against recombinant proteins INH-α or AMH could promote LH hormone secretion, regulate follicle development and decrease the broodiness rate. Also, active immunization with a recombinant-derived goose PRL protein might improve egg laying performance.

Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated autoimmune demyelinating disease of the central nervous system (CNS) that serves as an animal model of the human inflammatory demyelinating disease: multiple sclerosis. Acute EAE can be induced in the Lewis rat by active immunization with myelin basic protein (MBP) and complete Freund's adjuvant (CFA), or by the passive transfer of MBP­activated lymphocytes. The rats develop stereotyped neurological signs with a predictable temporal profile: ascending tail paralysis followed by hindlimb weakness and then occasionally forelimb weakness. They rapidly and spontaneously recover, so that by about 7 days after the onset of neurological signs there is no residual weakness. The process of spontaneous recovery is not yet fully understood, and many factors have been postulated to play a role, including endogenous corticosteroids, suppressor cells and nitric oxide. During clinical recovery, the apoptosis of inflammatory cells in the CNS, which involves T cells, B cells, macrophages and microglia, contributes to the resolution of inflammation in the CNS. After recovery from an episode of actively induced EAE, Lewis rats have generally been found to be resistant to the reinduction of active disease, and either resistant or susceptible to passively induced EAE. Rats that have recovered from passively induced EAE have been found by some authors to be fully susceptible to the reinduction of disease by active or by passive means, and by other authors to be resistant to the reinduction of disease by active or passive means. Various mechanisms have been postulated to account for the resistance to reinduction of EAE, especially the action of suppressor cells, but little attention has been given to the role of downregulatory factors within the target organ, the CNS.

Vaccination is expected to suppress COVID-19 infection. However, breakthrough infections have increased following vaccination because of the spread of variants of concern, notably Delta (B.1.617.2 lineage). Virological and serological data pertaining to post-vaccination infections are limited. Here, we conducted genome analysis determined the viral lineages that infected patients following vaccination. Changes in viral load, antibody levels, and viral antigen levels following infection were analyzed. At the time of infection, Delta-infected patients had a 6.2-fold and 12.3-fold higher viral load compared with Alpha and other lineages, respectively. Viral lineages (Delta:Alpha:Other) of infection were 0:12:0 in the fully vaccinated group, 1:11:0 in the partially vaccinated group, 9:16:0 in the shortly after vaccination group, and 254:229:165 in the unvaccinated group. Breakthrough infections occurred regardless of retention of high antibody titers following vaccination. At the time of diagnosis, Delta-infected patients showed high viral load with or without vaccination. However, no fully vaccinated patients developed severe disease, and the rapid increase in anti-spike antibodies occurred approximately 1 week after onset of symptoms. Concomitantly, a decrease in viral antigen levels was observed in fully vaccinated patients, shortening the time to negative result by approximately 2 days compared with unvaccinated patients. Collectively, even if breakthrough infection occurs, the rapid antibody response in fully vaccinated individuals contributes to prevention of severe disease, possibly because of suppression of viral replication.

We evaluated whether Denver neighborhoods with elevated rates of adult hospitalizations for laboratory-confirmed influenza had lower adult coverage with influenza vaccine. Overall vaccine coverage was low. Hospitalization rates were associated with demographic and socioeconomic characteristics. Active immunization of at-risk neighborhoods may be necessary to address disparities in influenza hospitalization rates.

The concept of adult immunization in general and maternal immunization specifically has been receiving an increased attention from clinicians and medical writers as new vaccines have come into the market. The benefit of vaccination in pregnancy is to protect (i) the mother from disease and (ii) the neonate from disease with passive maternal antibodies. Active immunization is the administration of an antigen, which may be a live attenuated organism, inactivated viruses, recombinant viral particles, purified proteins, bacterial capsular polysaccharides, or exotoxin derivatives (toxoids) with the projected effect of preventing, abbreviating, or ameliorating natural infection. An immunization history should be obtained at the first prenatal visit. In an ideal world, the patient should be immune to measles, mumps, rubella, tetanus, diphtheria, pertussis, poliomyelitis, varicella, and hepatitis A and B. Influenza is an acute febrile illness associated with headaches, migraines, upper airway respiratory complaints, and gastrointestinal symptoms.

Nosocomial infections caused by Acinetobacter baumannii (A. baumannii) nosocomial infections caused by Acinetobacter baumannii (A. baumannii) are considered as a global serious problem in hospitalized patients because of emerging antibiotic resistance. Immunotherapy approaches are promising to prevent such infections. In our previous study, five antigenic epitopes of outer membrane protein A (OmpA), as the most dangerous virulence molecule in A. baumanii, were predicted in silico. In this study, the investigators evaluated some immunological aspects of the peptides. Five peptides were separately injected into C5BL/6 mice; then the cytokine production (interleukin-4 and interferon-gamma) of splenocytes and opsonophagocytic activity of immunized serum were assessed. To identify the protective function of the peptides, animal models of sepsis and pneumonia infections were actively and passively immunized with selected peptides and pooled sera of immunized mice, respectively. Then, survival rates of them were compared with the non-infected controls. Based on the results, activated spleen cells in P127 peptide-immunized mice exhibited an increase level of IFN-γ compared with the other experimental groups, but not about the IL-4 concentration. The results of opsonophagocytic assay revealed an appropriate killing activity of produced antibodies against A. baumannii in a dose-dependent manner. Further, the survival rates of the mice under passive immunization with the immunized sera or active immunization with P127 peptide were significantly more than those in the control group. Moreover, the survival rate of the P127 peptide immunized group was considerably higher than that among the other peptide-immunized group. In conclusion, findings indicated that peptides derived from outer membrane protein-A can be used as a promising tool for designing the epitope-based vaccines against infections caused by A. baumannii.

Senecavirus A (SVA) is a newly porcine virus that has been detected in many countries since its first detection in pigs in Canada in 2007, and it remains endemic in many countries in Asia and America, which has become a substantial problem for the pig industry. Vaccination is a potentially effective strategy for the prevention and control of SVA infection. Our lab has developed a SVA vaccine candidate previously. In this study, the antibody response to the prepared vaccine in sows and their offspring was evaluated. Vaccination of sows with inactivated SVA vaccines during pregnancy elicited SVA-specific virus-neutralizing antibodies. Vaccination with a high dose of SVA vaccine followed a booster immunization contributed to a long-term duration of the persistence of maternally derived neutralizing antibodies (MDAs) in the milk of the sows (&gt, 14 days). In contrast, vaccination with a single low dose of SVA vaccine resulted in a short-term persistence of MDAs in the milk (2–7 days). The MDAs could be efficiently transferred from the sows to their offspring through the colostrum/milk but not the umbilical cord blood. The antibody titers and the duration of the persistence of MDAs in the offspring are highly associated with the antibody levels in the milk from the sows. Vaccination of sows with a booster dose of SVA vaccine resulted in a longer-lasting MDAs in their offspring (persisted for at least 90 days). However, vaccination with the single low dose of vaccine only brought about 42 days of MDAs persistence in their offspring. The effect of MDAs on active immunization with SVA vaccine in offspring was further evaluated, which showed that vaccination of the SVA vaccine in the presence of MDAs at the titer of ≈1:64 or less could overcome the MDAs’ interference and give rise to effective antibody response. This will help for establishing the optimal times and schedules for SVA vaccination in pigs.

Among the mechanisms by which tumor cells escape the immune surveillance, one is the interaction between programmed cell death protein 1 (PD-1) and its ligand programmed death-ligand 1 (PD-L1). Inhibition of the PD-1/PD-L1 pathway with monoclonal antibodies as immune checkpoint inhibitors targeting PD-1 or its ligand, PD-L1, represents a milestone in cancer therapy. The application of these antibodies, however, suffers from drawbacks including failure to show a response or benefit in a majority of patients following monotherapy or combination therapy, their frequent administration, and cost intensiveness. Small peptides capable of interfering with PD-1/PD-L1 interaction represent interesting alternatives to antibody-based immune checkpoint inhibitors. Moreover, peptides representing PD-1 or PD-L1 sequences can be used in active immunization approaches to induce antibodies that enhance antitumor immunity by effectively preventing PD-1-mediated inhibition in the host. Importantly, such peptides can readily be combined with peptides derived from cancer antigens to effectively induce an antitumor immune response. In this review, we have summarized the recent developments in the use of small molecules and peptides either to directly block PD-1/PD-L1 interaction, or in vaccination approaches to induce antibody responses stimulating anticancer immunity by blocking PD-1-mediated T-cell inhibition., Highlights • Blockade of the PD-1/PD-L1 interaction by antibodies as immune checkpoint inhibitors (ICIs) is a milestone in immunotherapy. • Treatment by ICIs has disadvantages, like frequent administration, low response in some patients, and cost intensiveness. • Direct blockade by small compounds or vaccination by peptides are two promising alternatives to the treatments with ICIs. • Such alternatives may pave the way to therapeutics which could be used as monotherapy, or in combination with ICIs.

Background: Chronic Hepatitis B (CHB) remains a major problem for global public health. Viral persistence and immune defects are the two major reasons for CHB, and it was hypothesized that based on a transient clearance of serum viral DNA and HBsAg “window stage”, active immunization against hepatitis B virus (HBV) might initiate effective host immune responses versus HBV to achieve functional cure of CHB. Methods: Two experimental mouse models that mice hydrodynamic injected HBV DNA or infected with recombinant AAV/HBV were used. The “sandwich” therapeutic effect by using a potent human anti-HBsAg neutralizing monoclonal antibody (G12) in combination with antiviral drug tenofovir disoproxil fumarate (TDF), followed by active immunization with HBsAg-HBsAb (mYIC) was evaluated. Findings: A single G12 injection rapidly cleared serum HBsAg in HDI-HBV carrier mice, with a synergistic effect in decreasing viral DNA load when TDF was given orally. When both serum viral DNA and HBsAg load became low or undetectable, mYIC was administered. A more effective clearance of viral DNA and HBsAg was observed and serum HBsAb was developed only in these “sandwich”-treated mice. Efficient intrahepatic anti-HBV immune responses were also observed in these mice, including the formation of aggregates of myeloid cells with CD8+ T cells and increased TNF-α, granzyme B production. Interpretation: The “sandwich” combination therapy not only efficiently decreased HBsAg and HBV DNA levels but also induced effective cellular and humoral immunity, which may result in functional cure of CHB. Keywords: Chronic hepatitis B, HBsAb, TDF, HBsAg-HBsAb immune complex, Liver CD8+ T cells

Brucellosis is a worldwide bacterial zoonosis caused by Brucella spp. No approved vaccine is available for human use against the disease. In this study, outer membrane vesicles (OMVs) from a Brucella melitensis biovar 1 human isolate obtained in Iran were used to immunize BALB/c mice (n = 12) by 2 intramuscular injections with a 2-week interval. Another group of 12 mice was used as non-vaccinated controls. Two weeks after the last vaccination, six mice of each group were sacrificed, and proliferation and interferon gamma (IFNγ) production responses of their splenocytes were evaluated following in vitro stimulation with killed Brucella cells. The other mice were challenged with the virulent B. melitensis isolate. Two weeks later, mice were killed and spleens were cultured to determine the number of the challenge strain. The results showed proliferative response and IFNγ production of splenocytes from vaccinated mice (stimulation index: 2.18 ± 0.57, and 1519.35 ± 10.70 pg/mL, respectively) were significantly higher than those of control mice (stimulation index: 1.02 ± 0.02, and 210.01 ± 17.58 pg/mL, respectively). Numbers of the challenge strain in spleens of vaccinated mice were also significantly less than those in the controls with 1.6 units of protection. Our study revealed vaccination with OMVs of the B. melitensis isolate could induce specific immune responses and protection against infection in the mouse model suggesting their potential application for active immunization against brucellosis.

Active immunization is a crucial colony-level pathogen defense to improve the survival of eusocial termites, which limits the lethal effect of biopesticides for termite control. Here, we report a possible strategy for RNAi-mediated metabolic disorders, which causes reduction in insect pathogen defense and might facilitate the foundation of nontoxic and sustainable pest control methods. Isocitrate dehydrogenase (IDH) was significantly upregulated by active immunization in termites, but its regulatory mechanism has yet to be well understood. We found that dsIDH-injected termites exhibited significantly reduced IDH at mRNA and protein levels and altered levels of isocitrate and NADH, indicating the impaired NAD+-IDH reaction. IDH-silenced termites displayed metabolic disorders, which was implied by significant changes in several metabolites from the carbohydrates and amino acids. When grooming toward fungus-exposed termites, IDH-silenced nestmates showed a significant upregulation of four apoptosis-related genes and caspase 3 activity, and hence the significantly increased rate of apoptosis. These physiological changes led to more apoptotic cell death in different body parts of the nestmates. In particular, more apoptotic cells increased disease susceptibility of the nestmates as revealed by growth of the significantly increased number of colony-forming units from dissected gut contents. Furthermore, the IDH-silenced nestmates exhibited lower antifungal activity and higher mortality, suggesting that IDH downregulation disrupted active immunization against fungal pathogens in termites. These findings illustrated the metabolic regulation of active immunization and provide a sound foundation for enhancing the impact of biopesticides by reducing the pathogen defense of hosts.

Dengue virus (DENV) causes a range of illness, including dengue fever, dengue hemorrhagic fever, and dengue shock syndrome. DENV nonstructural protein (NS) 1 has been considered to be a desirable vaccine candidate for its ability to induce Ab and complement-dependent cytolysis of DENV-infected cells as well as to block the pathogenic effects of NS1. However a potential drawback of NS1 as a vaccine is that anti-DENV NS1 Abs can lead to endothelial cell damage and platelet dysfunction by antigenic cross-reactivity. Therefore, we modified the DENV NS1 by replacing the C-terminal cross-reactive epitopes with the corresponding region of Japanese encephalitis virus NS1 to generate a chimeric DJ NS1 protein. Active immunization with DJ NS1 induced a strong Ab response. To enhance cellular immunity, we further combined DJ NS1 with DENV NS3 to immunize mice and showed activation of Ag-specific CD4+ and CD8+ T cells in addition to Ab responses. We further detected NS3-specific CTL activities as well as CD107a expression of effector cells. Importantly, the protective effects attributed by DJ NS1 and NS3 immunization were demonstrated in a DENV-infected mouse model by reduced viral titers, soluble NS1 levels, mouse tail bleeding time, and vascular leakage at skin injection sites. Collectively, the results from this study reveal the humoral and cellular immune responses and the protective effects conferred by DJ NS1 and NS3 immunization in the mouse model of DENV infection and provide a potential strategy for dengue vaccine design.

Introduction: Alzheimer's disease (AD) vaccination is one of the last therapeutic options after two decades of stagnation in terms of drug development. About 140 (85%) immunization procedures against Aβ deposition and 25 (15%) against Tau have been reported, but no Food and Drug Administration approval of any AD vaccine has been achieved. This might be attributed to deficient pathogenic targets, inappropriate models, defective immunotherapeutic procedures, and inadequate clinical trial design.Areas covered: The issues covered include the following: AD pathogenic mechanisms, rationale for active and passive immunization, vaccine targets, anti-Aβ/Tau vaccines, vaccine technologies, animal models, and clinical trials.Expert opinion: A vaccine against AD is technically feasible; however, important methodological aspects should be changed for a tentative clinical success, including (i) the development of multitarget AD immunotherapies; (ii) the optimization of antibody titers and epitopes; (iii) the pharmacogenetic/pharmacoepigenetic validation of the immunization procedure; (iv) the prophylactic treatment of genetically stratified patients at a pre-symptomatic stage; and (v) the definition of primary endpoints in prevention, based on objective/multifactorial biomarkers. Even with exquisite protocols, a successful vaccine would be potentially useful in at most 20-30% of defined cases, according to the genetic, epigenetic, and pharmacogenetic background of AD patients.

Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

Macrophages have been recognized as a vital factor that can promote renal fibrosis. Previously we reported that the EGFR mimotope could alleviate the macrophage infiltration in the Sjögren's syndrome-like animal model. In current study, we sought to observe whether the active immunization induced by the EGFR mimotope could ameliorate renal fibrosis in the murine Unilateral Ureteral Obstruction (UUO) model. A series of experiments showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, α-SMA and collagen I and alleviate the infiltrations of F4/80+ macrophages in UUO model. Meanwhile, the EGFR mimotope immunization could inhibit the EGFR downstream signaling. Additionally, the frequency of and F4/80+CD9+/FAS+ macrophages significantly increased in spleen after the EGFR mimotope immunization. These evidence suggested that the EGFR mimotope could alleviate renal fibrosis by both inhibiting EGFR signaling and promoting macrophages apoptosis.

The accumulation of skatole in fat tissue is one of the predominant factors, causing boar taint. The present study was aimed to understand the mechanism whereby active immunization against GnRH (immunocastration) eliminates skatole in boars. Thirty-six boars were assigned within litter into three groups (n = 12): control, surgically castrated, or immunized against GnRH at 10 wk of age (with a booster 8 wk later). Faecal and blood samples (for skatole and skatole-regulatory hormone profiles) were collected at 4-wk intervals until boars were slaughtered (26 weeks). Immunocastration reduced (P 0.05) serum levels of androstenone, 17β-estradiol and IGF1 especially after the booster immunization, and down-regulated (P 0.05) mRNA expressions of both IGF1 and IGF1receptor (IGF1R) in mucosa of ileum as well as colon at slaughter. Compared to intact controls, immunocastration substantially decreased (P 0.05) faecal skatole contents subsequent to the decrease of serum IGF1 levels, which persisted in boars after surgical castration. In parallel with the decreased formation of skatole in the intestine, levels of skatole in serum and then in fat tissue were also decreased (P 0.05). On the other hand, deprivation of testicular steroids, especially androstenone and 17β-estradiol accelerated skatole degradation metabolism in the liver by increasing (P 0.05) hepatic CYP2E1, CYP2A, CYP2C49 and CYB5A expressions. Collectively, our results suggested that immunocastration decreased skatole formation in the intestine and meanwhile accelerated skatole degradation metabolism in the liver, resultantly eliminating skatole accumulation in male pigs. Decreased intestinal skatole formation by immunocastration appeared to be associated with the attenuated actions of IGF1 on the turnover of both ileal and colon mucosa.

ObjectivesVaccination against feline herpesvirus-1 (FHV-1) is recommended for all cats. However, it is unknown how adult healthy cats with different pre-vaccination antibodies respond to FHV-1 vaccination in the field. The aim of the study was to determine the prevalence of neutralising antibodies against FHV-1 in healthy adult cats and the response to FHV-1 vaccination within 28 days of vaccination.MethodsOne hundred and ten cats (⩾1 year of age) that had not received a vaccination within the past 12 months were vaccinated with a combined FHV-1 vaccine. Antibodies against FHV-1 were determined before vaccination (day 0), on day 7 and day 28 by serum neutralisation test. Uni- and multivariate statistical analyses were used to determine factors associated with the presence of pre-vaccination antibodies and response to vaccination.ResultsPre-vaccination neutralising antibody titres (⩾10) were present in 40.9% of cats (45/110; 95% confidence interval [CI] 32.2–50.3); titres were generally low (range 10–640). Antibody response to vaccination (⩾four-fold titre increase) was observed in 8.3% (9/109; 95% CI 4.2–15.1). Cats ⩾2 years of age were more likely to have pre-vaccination neutralising antibodies than cats aged between 1 and 2 years (odds ratio [OR] 24.619; P = 0.005). Cats from breeders were more likely to have pre-vaccination neutralising antibodies than privately owned cats (OR 7.070; P = 0.007). Domestic shorthair cats were more likely to have an at least four-fold titre increase vs purebred cats (OR 11.22; P = 0.027).Conclusions and relevanceMany cats have no detectable neutralising antibodies against FHV-1 despite previous vaccinations and fail to develop a ⩾four-fold titre increase after vaccination. This is likely because older cats and cats with a higher FHV-1 exposure risk are more likely to get infected with FHV-1 and thus to have FHV-1 neutralizing antibodies. Purebred cats more often fail to develop a ⩾four-fold titre increase after vaccination.

Maternal immunization with pertussis acellular vaccine (Tdap) is an intervention that provides protection to newborns. However, it has been reported that high maternal antibody levels may adversely affect the immune response of infants after active immunization. In this study, we evaluated neonatal passive acquisition of pertussis-specific antibodies and their influence on the neonatal cell-mediated immune response. Pregnant women were either vaccinated with Tdap vaccine (case group, n = 66) or received no vaccine (control group, n = 101). Whole-cell Bordetella pertussis (Bp), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN)-specific serum IgG were quantified in paired maternal-cord sera, and Bp- and PT-specific IgA were evaluated in colostrum by ELISA. Ex vivo neonatal blood lymphocyte responsiveness after Bp stimulation was assessed in case (n = 17) and control (n = 15) groups using flow cytometry to detect proliferation, cytokine production and activation phenotype of lymphocytes in the context of high specific IgG acquired after maternal vaccination. Anti-Bp, PT, FHA and PRN IgG concentrations in maternal and cord sera from case group were higher than those in control group with positive correlation indexes in both groups for all pertussis antigens. The control group presented higher placental transfer ratios of specific antibodies and, in the case group, vaccination between 26 and 31 gestation weeks was associated with the best placental transfer ratios. Specific IgA concentrations in colostrum were not affected by vaccine status. Whole blood assays revealed that newborns responded to Bp stimulation with higher expression of CD40L, CD69 and CD4+ T cell proliferation compared to unstimulated cells, and a lower Th1 response, while a preserved Th2 response compared to adults, but there were no differences between the neonatal groups for any of the studied parameters. Our results indicate that higher pertussis-specific IgG levels in newborn sera after maternal vaccination do not affect the neonatal ex vivo cell-mediated immune response.

Staphylococcus aureus normally colonizes the nasal cavity and pharynx. After breaching the normal habitat, the organism is able to cause a number of infections at any site of the body. The development of antibiotic resistance has created a global challenge for treating infections. Therefore, protection by vaccines may provide valuable measures. Currently, several vaccine candidates have been prepared which are either in preclinical phase or in early clinical phase, whereas several candidates have failed to show a protective efficacy in human subjects. Approaches have also been made in the development of monoclonal or polyclonal antibodies for passive immunization to protect from S. aureus infections. Therefore, in this review we have summarized the findings of recently published scientific literature to make a concise report.

Background Group B streptococcus (GBS) causes serious diseases in newborn infants, often resulting in lifelong neurologic impairments or death. Prophylactic vaccination of pregnant women prior to delivery could provide comprehensive protection, as early onset and late-onset disease and maternal complications potentially could be addressed. Methods Capsular polysaccharide conjugate vaccine GBS6 was designed using surveillance data yielded by whole-genome sequencing of a global collection of recently recovered GBS isolates responsible for invasive neonatal GBS disease. Capsular polysaccharides were isolated, oxidized using sodium periodate, and conjugated to CRM197 by reductive amination in dimethyl sulfoxide. Immune responses in mice and rhesus macaques were measured in a multiplex Luminex immunoglobulin G (IgG) assay and opsonophagocytic activity assays. Results The optimized conjugates were immunogenic, alone and in combination, in mice and rhesus macaques, inducing IgG antibodies that mediated opsonophagocytic killing. Active immunization of murine dams with GBS6 prior to mating resulted in serotype-specific protection of pups from a lethal challenge with GBS. Protection following passive administration of serotype-specific IgG monoclonal antibodies to dams demonstrated conclusively that anticapsular polysaccharide IgG alone is sufficient for protection. Conclusions The findings support the ongoing clinical evaluation of maternal GBS6 vaccination as a potential alternative method to prevent GBS disease in infants., Six-valent capsular polysaccharide conjugate vaccine GBS6 for the prevention of neonatal Group B Streptococcal (GBS) infections was evaluated in preclinical models. Vaccination with GBS6 or administration of serotype-specific IgG to pregnant dams protected pups against lethal challenges with GBS.

Human infections caused by the opportunist pathogens Burkholderia cepacia complex and Pseudomonas aeruginosa are of particular concern due to their severity, their multiple antibiotic resistance, and the limited eradication efficiency of the current available treatments. New therapeutic options have been pursued, being vaccination strategies to prevent or limit these infections as a rational approach to tackle these infections. In this review, immunization and immunotherapy approaches currently available and under study against these bacterial pathogens is reviewed. Ongoing active and passive immunization clinical trials against P. aeruginosa infections is also reviewed. Novel identified bacterial targets and their possible exploitation for the development of immunization and immunotherapy strategies against P. aeruginosa and B. cepacia complex and infections are also presented and discussed.

Passive immunization with polyclonal hyper immunoglobulin (HIG) therapy represents a proven strategy by transferring immunoglobulins to patients to confer immediate protection against a range of pathogens including infectious agents and toxins. Distinct from active immunization, the protection is passive and the immunoglobulins will clear from the system; therefore, administration of an effective dose must be maintained for prophylaxis or treatment until a natural adaptive immune response is mounted or the pathogen/agent is cleared. The current review provides an overview of this technology, key considerations to address different pathogens, and suggested improvements. The review will reflect on key learnings from development of HIGs in the response to public health threats due to Zika, influenza, and severe acute respiratory syndrome coronavirus 2.

Background: Pasteurellosis is an economically important disease of livestock worldwide and vaccination is effective mean to control the disease outbreaks. One of alternative method for vaccine preparation could be the use of lytic phages as bacterial inactivating agents and employing “phage lysate immunogen” as an immunizing agent. Therefore, the study was undertaken to explore the protective immune response of novel phage lysate vaccine against Pasteurella multocida. Methods: A phage lysate vaccine of Pasteurella multocida was prepared using isolated lytic phage and subjected to vaccine response study in rabbits. In this experiment, two mouse fixed-dose of lysate was used and the prophylactic efficacies of lysates were evaluated in rabbits by passive mouse protection test (PMPT), western blotting and direct virulent challenge.Result: Passive transfer of antibodies to mice using post-immunization sera of rabbits protected the animals against the challenge with A: 1 strain (75%) and B: 2 strain (50%). In western blotting, a total number of 4 bands were observed in the region between 130 kDa to 25 kDa in the protein of the phage lysate. The study suggested the significance increase in humoral immunity by phage lysate in murine Pasteurellosis.

Breast cancer cells often metastasize to bone. Accumulating evidence suggests that inhibiting the receptor activator of nuclear factor-κB ligand (RANKL) not only leads to reduced bone metastasis of breast cancer but also has antitumoral effects. Here, we used mutant receptor activator of nuclear factor-κB ligand (RANKLM) as a vaccine for active immunization to induce antibodies for immunotherapy of bone metastatic cancer. We investigated whether anti-RANKL antibodies inhibit osteolytic bone metastasis in vitro and in a murine model. MC3T3 cells stimulated by MDA-MB-231 culture medium secreted growth differentiation factor-15 (GDF-15), which induced the nuclear factor-κB signaling cascade. In addition, RANKLM treatment-induced reduction of intraosseous growth of MDA-MB-231 cells correlated with decreased GDF-15 expression, a reduced number of osteolytic lesions, and slower tumor progression. In addition, vaccination with RANKLM led to significant improvement in overall survival and skeletal metastasis in tumor-bearing mice. Induction of anti-RANKL antibodies by RANKLM decreased GDF-15 production by deactivating nuclear factor-κB signaling, which in turn inhibited metastasis of MDA-MB-231 cells to bone. Taken together, the results demonstrate a role for RANKLM immunization in preventing bone metastasis of breast cancer.

The aim of this study was to evaluate the effect of active immunization against GnRH in Nelore (Bos indicus) cows repeatedly used as oocyte donors that developed chronic cystic ovarian disease (COD). In the first experiment, ovarian and uterine features were first compared between COD cows (n = 15) and healthy cows (n = 22, cycling control group) from the same breed and herd. Cows with COD had a greater number of large (P 0.0001) and medium follicles (P 0.01) but lesser small follicles (P 0.05) than cycling controls. Mucometra was diagnosed in 73.3% of COD cows, but in none of the controls. No difference in average thickness of the endometrium was detected between groups; however, endometrial thickness and mucometra score were negatively correlated (R = -0.73, P = 0.0029) in COD cows. In the second experiment, COD cows were randomly allocated into two experimental groups, which received two 1.0 mL SC injections of either an anti-GnRH vaccine (COD immunized group, n = 8) or saline (COD control group, n = 7), given 28 days apart. Cows were examined weekly by transrectal ultrasonography during nine consecutive weeks after the first injection to evaluate the number and distribution of follicles among size classes, endometrial thickness, and presence of clinical mucometra. Vaccination against GnRH resulted in a progressive suppression of follicle growth and a reduction in the average size of the largest follicle, as well as in the number of large follicles (P 0.01) in COD immunized cows compared with COD controls from week 7 onwards. Conversely, the number of small follicles in the COD immunized group increased after week 5 and was greater (P = 0.0023) than controls on week 9. Endometrial thickness and mucometra score were not affected (P 0.05) by immunization against GnRH. In the third experiment, the COD immunized cows with effective suppression of follicle growth four weeks after the 2nd injection (n = 6) were submitted to three consecutive ovum pick-up (OPU) sessions (weeks 10, 11, and 12) for in vitro embryo production (IVEP). Cumulus-oocyte complexes (COC) collected from slaughterhouse ovaries were used as controls for IVEP. COD cows with produced 25.0 ± 3.8 COC per OPU session with no apparent detrimental effect of anti-GnRH vaccine on oocyte developmental potential in vitro, i.e., we observed similar cleavage rate (P = 0.5914) and greater blastocyst rate (P = 0.0177) in immunized cows compared with COC from slaughterhouse controls. Finally, in the fourth experiment wave emergence and follicular dynamics after follicle ablation were compared between COD immunized cows with effective suppression of follicle growth and a subset (n = 6) of the cycling, control group. No follicles grew beyond 4 mm diameter after follicle ablation in the COD immunized group, whereas a normal follicular wave emergence occurred in cycling controls. Antral follicle count was similar between cycling controls and COD immunized groups at 24 h and 96 h post-follicle ablation (P 0.05), but greater in cycling controls at 48 h and 72 h post-follicle ablation (P 0.05). In summary, our results suggest that active immunization against GnRH is effective to induce the regression of follicular cysts as well as increase the number of small follicles growing on the ovaries, in oocyte donors diagnosed with chronic COD, with no apparent negative effect on oocyte developmental potential in vitro.