Miller fisher syndrome with positive anti-GQ1b/GT1a antibodies associated with COVID-19 infection:A case report

BACKGROUND Miller fisher syndrome(MFS)is a variant of Guillain-Barrésyndrome,an acute immune-mediated peripheral neuropathy that is often secondary to viral infections.Anti-ganglioside antibodies play crucial roles in the development of MFS.The positive rate of ganglioside antibodies is exceptionally high in MFS patients,particularly for anti-GQ1b antibodies.However,the presence of other ganglioside antibodies does not exclude MFS.CASE SUMMARY We present a 56-year-old female patient who suddenly developed right blepharoptosis and progressively worsening vision in both eyes.There were flu symptoms prior to onset,and a coronavirus disease 2019 test was positive.On physical examination,the patient exhibited bilateral extraocular muscle paralysis,weakened reflexes in both limbs,and impaired coordination.The cerebrospinal fluid examination results showed no obvious abnormalities.Bilateral peroneal nerve F-waves were not extracted.Serum anti-GD1b IgG and anti-GT1a IgG antibodies were positive.The patient received intravenous methylprednisolone(1000 mg/day),with the dosage gradually decreased.Additionally,intravenous high-dose immunoglobulin treatment was administered for 5 days(0.4 g/kg/day)from day 2 to day 6 of hospitalization.The patient’s symptoms improved after treatment with immunoglobulins and hormones.CONCLUSION Positive ganglioside antibodies may be used as supporting evidence for the diagnosis;however,the diagnosis of MFS is more reliant on clinical symptoms.

An overview on CV2/CRMP5 antibody-associated paraneoplastic neurological syndromes

Paraneoplastic neurological syndrome refers to certain malignant tumors that have affected the distant nervous system and caused corresponding dysfunction in the absence of tumor metastasis.Patients with this syndrome produce multiple antibodies,each targeting a different antigen and causing different symptoms and signs.The CV2/collapsin response mediator protein 5(CRMP5)antibody is a major antibody of this type.It damages the nervous system,which often manifests as limbic encephalitis,chorea,ocular manifestation,cerebellar ataxia,myelopathy,and peripheral neuropathy.Detecting CV2/CRMP5 antibody is crucial for the clinical diagnosis of paraneoplastic neurological syndrome,and anti-tumor and immunological therapies can help to alleviate symptoms and improve prognosis.However,because of the low incidence of this disease,few repo rts and no reviews have been published about it so far.This article intends to review the research on CV2/CRMP5antibody-associated paraneoplastic neurological syndrome and summarize its clinical features to help clinicians comprehensively understand the disease.Additionally,this review discusses the curre nt challenges that this disease poses,and the application prospects of new detection and diagnostic techniques in the field of paraneoplastic neurological syndrom e,including CV2/CRMP5-associated paraneoplastic neurological syndrome,in recent years.

Renal Vein Thrombosis Suggestive of Extramembranous Glomerulonephritis Associated with Sjögren’s Syndrome (Case Report)

Introduction: Glomerular damage during Gougerot-Sjgren syndrome is much rarer than interstitial damage, and is essentially extra-membranous and membrano-proliferative glomerulonephritis. Observation: We report the case of a 44-year-old woman with primary Sjgrens syndrome, confirmed by clinical dryness syndrome, positive anti-SSA and anti-SSB antibodies, and a salivary gland biopsy revealing grade 4 lymphocytic sialadenitis according to CHISHOLMs classification. Later, the patient developed nephrotic syndrome, along with hypertension. Renal function remained normal with a creatinine level of 9.3 mg/l, and hematuria was absent. Only antinuclear antibodies tested positive, while anti-PLA2R antibodies were negative. A renal biopsy was performed, which was complicated on the same day by hemodynamic instability with hematuria. Renal CT scan with contrast injection revealed a posterior perirenal hematoma without contrast extravasation. Additionally, bilateral renal vein thrombosis was incidentally discovered, suggesting extramembranous glomerulonephritis. The patients hemodynamic status stabilized after fluid resuscitation with isotonic saline solution (0.9%), without the need for blood transfusion. Renal biopsy confirmed extramembranous glomerulonephritis with interstitial fibrosis and minimal tubular atrophy. The initial etiological assessment was negative. The patient was started on oral corticosteroids, angiotensin-converting enzyme inhibitors, and therapeutic anticoagulation for renal vein thrombosis. The patients condition improved, with the disappearance of the syndrome and spontaneous regression of the hematoma. Discussion: The association of nephrotic syndrome and renal vein thrombosis primarily suggests glomerulopathy, in particular extra-membranous glomerulonephritis. Sjgrens syndrome can be associated with extra-membranous glomerulonephritis without being its direct cause. Like, it is possible that it is a cause of glomerulonephritis, essentially extra membranous and membrano-proliferative. Conclusion: Sjgrens syndrome is generally underestimated cause of glomerulonephritis, which should be considered in cases of extra-membranous glomerulonephritis.

Development and application of antibody microarray for white spot syndrome virus detection in shrimp

Detecting white spot syndrome virus （WSSV） in shrimp in high efficiency and veracity is important for disease prevention in aquaculture. Antibody-based mieroarray is a novel proteomic technology that can meet the requirements. In this study, we developed an antibody microarray for WSSV-detection in a specific and parallel way at multiple samples. First, seven slides each with different modifications were characterized by atomic force microscope, and were compared in the efficiency of immobilizing proteins. Of the seven, 3-dimensional structured agarose gel-modified slides were chosen appropriate for the microarray for having higher signal value and superior spot size. A purified rabbit anti-WSSV antibody was arrayed as the capture antibody of the microarray on the agarose gel-modified slides, and then the mieroarray slides were incubated in the tissue homogenate of sampled shrimp and the antibody-antigen complex was detected by Cy3-conjugated anti-WSSV monoclonal antibody. The results were measured by a laser chipscanner and analyzed with software. To obtain satisfied fluorescence signal intensity, optimal conditions were searched. The detection limit of the antibody microarray for WSSV is 0.62μg/mL, with a woven long shelf life for 6 months at 4℃ or 8 months at -20℃. Furthermore, concordance between antibody microarray and traditional indirect ELISA reached 100% for WSSV detection. These results suggest that the antibody microarray could be served as an effective tool for diagnostic and epidemiological studies of WSSV.

Antiphospholipid antibody syndrome and pregnancy

Recurrent foetal loss in early and late stages of pregnancy is a common problem of women affected by anti-phospholipid antibody syndrome. The therapeutic scheme consisting of associating aspirin and heparin has shown an improvement of the prognosis for the next pregnancies. We report 3 cases of anti-phospholipid antibody syndrome and pregnancy, and we underline the clinical, therapeutic and prognosis features of this syndrome.

Application of GP5 Protein to Develop Monoclonal Antibody against Porcine Reproductive and Respiratory Syndrome Virus

In this study, a panel of monoclonal antibodies （mAbs） against Porcine reproductive and respiratory syndrome virus（PRRSV）, named as 8C9 and4B4, were produced by fusing SP2/0 myeloma cells and spleen cells of BALB/c mice immunized with the PRRSV （TCID50=5.5）, screened by the indirect ELISA and subjected to several limiting dilutions, mAbs were then identified by biological characterization. Among the two fusion cell strains, 8C9 belonged to the IgG1 subclass and 4B4 belonged to the IgG2a subclass. The titers in cell culture supematant and abdomen liquor reached to 1：104and 1：105, respectively. The specificity test indicated that the two cells had specific reactions for the PRRSV and GP5 protein respectively, and no reaction with Classical swine fever virus （CSFV） or Swine vesicular disease virus （SVDV）. The molecular weights of the heavy chain and light chain were about 45.0 kDa and 25.0 kDa, respectively. In neutralization activity tests, the results showed that the prepared mAb 4B4 can protect 50% of cells with no CPE in dilution up to 1：512, but mAB 8C9 has no neutralization activities to PRRSV.

Screening for celiac disease in Down's syndrome patients revealed cases of subtotal villous atrophy without typical for celiac disease HLA-DQ and tissue transglutaminase antibodies

A1M： To investigate the prevalence of celiac disease （CD） as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down＇s syndrome （DS） patients. METHODS： Immunoglobulin A （IgA） and G （IgG） type anti-gliadin antibodies （AGA）, IgA type anti-tissue transglutaminase （tTG） antibodies （anti-tTG） with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies （EHA） by indirect immunofiuoresence test. HLA-DQA1＊0501/DQB1＊0201 （DQ2） was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS： 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % [gA EMA （all positive for anti-tTG with human tTG）. Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1＊0S01/DQB1＊0201 and anti-tTG and EMA i.e. typical for CD markers （this case also fulfilled the ESPGHAN diagnostic criteria）, but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1＊0S01/DQB1＊0201 and IgA anti-tTG （EMA） were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % （95 % of confidence interval [CI]： 0.1-5.9 %）. CONCLUSION： We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD （with atypical immunopathogenesis） or some other immune enteropathy, requires further investigations.

Blockade of Rho-associated kinase prevents inhibition of axon regeneration of peripheral nerves induced by anti-ganglioside antibodies

Anti-ganglioside antibodies are associated with delayed/poor clinical recovery in Guillain-Barrèsyndrome,mostly related to halted axon regeneration.Cross-linking of cell surface gangliosides by anti-ganglioside antibodies triggers inhibition of nerve repair in in vitro and in vivo paradigms of axon regeneration.These effects involve the activation of the small GTPase Rho A/ROCK signaling pathways,which negatively modulate growth cone cytoskeleton,similarly to well stablished inhibitors of axon regeneration described so far.The aim of this work was to perform a proof of concept study to demonstrate the effectiveness of Y-27632,a selective pharmacological inhibitor of ROCK,in a mouse model of axon regeneration of peripheral nerves,where the passive immunization with a monoclonal antibody targeting gangliosides GD1a and GT1b was previously reported to exert a potent inhibitory effect on regeneration of both myelinated and unmyelinated fibers.Our results demonstrate a differential sensitivity of myelinated and unmyelinated axons to the pro-regenerative effect of Y-27632.Treatment with a total dosage of 9 mg/kg of Y-27632 resulted in a complete prevention of anti-GD1a/GT1b monoclonal antibody-mediated inhibition of axon regeneration of unmyelinated fibers to skin and the functional recovery of mechanical cutaneous sensitivity.In contrast,the same dose showed toxic effects on the regeneration of myelinated fibers.Interestingly,scale down of the dosage of Y-27632 to 5 mg/kg resulted in a significant although not complete recovery of regenerated myelinated axons exposed to anti-GD1a/GT1b monoclonal antibody in the absence of toxicity in animals exposed to only Y-27632.Overall,these findings confirm the in vivo participation of Rho A/ROCK signaling pathways in the molecular mechanisms associated with the inhibition of axon regeneration induced by anti-GD1a/GT1b monoclonal antibody.Our findings open the possibility of therapeutic pharmacological intervention targeting Rho A/Rock pathway in immune neuropathies associated with the presence of anti-ganglioside antibodies and delayed or incomplete clinical recovery after injury in the peripheral nervous system.

Study and Application of Monoclonal Antibodies against Virus of Haemorrhagic Fever with Renal Syndrome

This paper summarizes the study and application of monoclonal antibodies (McAbs)against haemorrhagic fever with renal syndrome (HFRS) virus in our department over the past sever-al years. The following six points are discussed: (1) establishment and characterization of thehybridoma cell lines secreting McAbs against HFRS virus and hemagglutinin of the virus: (2) theantigenic analysis of HFRS viruses in China by McAbs: (3) purification and application of theMcAbs: (4) purification and characterization of HFRS virus 50K stnactural protein by McAba-affini-ty chromatography and the McAbs possessing different characteristics: (5) detection of HFRS virusantigen in peripheral blood lymphocytes from HFRS patients by the McAb-IFAT; and (6)development of McAb-ELISA indirect sandwich methods, and detection of HFRS virus antigen andIgM, IgG and/or HI antibodies in human and animals. The results of the studies show that theMcAbs can be used for early diagnosis, epidemiological investigation, preparation of vaccine andimmunotherapy of HFRS.

Generation of Monoclonal Antibody to Porcine Reproductive and Respiratory Syndrome Virus GP4 Protein and Identification of Its Minic Epitopes

Porcine reproductive and respiratory syndrome virus(PRRSV)GP4 protein was prokaryotically expressed,and used as an antigen to immunize six-week-old BALB/c female mice.With conventional cell fusion method,an anti-PRRSV GP4 protein monoclonal antibody(Mab)5F12 was successfully prepared.It was identified as IgG2b subclass and had better stability and specificity,which not only responded with recombinant PRRSV GP4 protein,but also with PRRSV.Phage display technique had varieties of applications,in particular,the identification of key antigen epitopes for the development of therapeutic and diagnostic reagents and vaccines.In this study,Mab-5F12 was used as the target for biopanning a 12-mer phage random peptide library.After four rounds of biopanning,two phage-displayed peptides,named P-A and P-G(AKFEVCSPVVLG and GVNQENMLHFSF)were identified that recognized Mab-5F12 specifically.Sequence analysis showed that one or more of the peptides exhibited partial sequence similarity to the native GP4 protein sequence,which corresponded to 69-80 and 84-95 aa segments of the HP-PRRSV GP4 protein.Furthermore,real-time quantitative RT-PCR and indirect immunofluorescence assay indicated consistently the abilities of P-A and P-G to block viral infection in Marc-145 cells and they could function as antiviral agents for PRRSV.

Automatic Evaluation of Test Strips for Anti-Ganglioside Antibodies in Patients with Guillain-BarréSyndrome Using EUROLineScan Software

Campylobacter jejuni infection has been implicated in the pathogenesis of Guillain-Barré syndrome (GBS) due to production of humoral immune response against neural antigens. A case-control study was performed in a tertiary care teaching hospital for the estimation of anti-ganglioside antibodies in GBS patients and their controls. Blood samples were collected from 59 GBS cases, 58 neurological controls (NC) and 60 non-neurological control (NNC) patients for automatic estimation of IgG and IgM antibodies to seven gangliosides using EUROLineScan software. Antibodies of IgG class for GM1 were highly significant in GBS (p = 0.000) and NC (p = 0.031) compared to NNC. However GBS group was not significant (p = 0.413) compared to NC. For GM2 ganglioside, GBS and NC groups were significant (p = 0.000) compared to NNC, but GBS group was not significant (p = 0.999) compared to NC. For GM3 ganglioside, GBS and NC groups were significant (p = 0.000) compared to NNC;but GBS group was insignificant (p = 0.858) compared to NC with similar trend for all other ganglioside antibodies. When IgM class of antibodies was evaluated for GM1, GBS group was not significant (p = 0.604) whereas NC group was significant (p = 0.000) compared to NNC. GBS group was not significant compared to NC (p = 0.011). The trend was the same for GM2 antibodies. For GM3, GBS group was significant (p = 0.010) and NC was near significant (p = 0.055) compared to NNC. However GBS group was not significant (p = 0.808) compared to NC. No groups were significant (p > 0.05) in relation to the remaining gangliosides except for GQ1b where GBS group (p = 0.001) and NC group were significant (p = 0.000) compared to NNC. GBS group was also significant (p = 0.001) compared to NC and NNC. Anti-gangliosides antibodies were present in highly significant levels in the GBS group, though they were also present in the non-paralytic neurological control patients compared to the non-neurological control group.

Paraneoplastic neurological syndrome with positive anti-Hu and anti-Yo antibodies:A case report

BACKGROUND Paraneoplastic neurological syndrome(PNS)is a rare complication in patients with cancer.PNS can affect the central,peripheral,autonomic nervous system,neuromuscular junction,or muscles and cause various neurological symptoms.Anti-Yo antibody-positive neurological paraneoplasms and anti-Hu antibodypositive neurological paraneoplasms are common,but coexistence of both types has not been described in the literature.CASE SUMMARY Here we present a rare case of paraneoplastic neuropathy occurring in both breast and lung cancers.A 55-year-old woman was admitted to our hospital with unsteadiness while walking.The patient had a history of breast cancer two years previously.Chest computed tomography revealed a 4.6 cm×3.6 cm mass in the right lung,which was diagnosed as small-cell lung cancer(SCLC).Blood test was positive for anti-Yo antibodies,and the cerebrospinal fluid was positive for both anti-Yo and anti-Hu antibodies,and the neurological symptoms were considered to be related to the paraneoplasm.The patient was treated with a course of intravenous immunoglobulin,without noticeable improvement.After being discharged from hospital,the patient underwent regular chemotherapy for SCLC and periodic reviews.The patient’s neurological symptoms continued to deteriorate at the follow-up visit in April 2021.CONCLUSION This case suggests the possibility of two types of tumors appearing simultaneously with two paraneoplastic antibodies.The clinical appearance of two or more paraneoplastic tumors requires additional attention.

Characterization and Diagnostic Use of a Monoclonal Antibody for VP28 Envelope Protein of White Spot Syndrome Virus

The gene encoding the VP28 envelope protein of White spot syndrome virus (WSSV) was cloned into expression vector pET-30a and transformed into the Escherichia coli strain BL21.After induction,the recombinant VP28 (rVP28) protein was purified and then used to immunize Balb/c mice for monoclonal antibody (MAb) production.It was observed by immuno-electron microscopy the MAbs specific to rVP28 could recognize native VP28 target epitopes of WSSV and dot-blot analysis was used to detect natural WSSV infection.Competitive PCR showed that the viral level was approximately 104 copies/mg tissue in the dilution of gill homogenate of WSSV-infected crayfish at the detection limit of dot-blot assay.Our results suggest that dot-blot analysis with anti-rVP28 MAb could rapidly and sensitively detect WSSV at the early stages of WSSV infection.

Antiphospholipid Antibody and Antiphospholipid Syndrome

Antiphospholipid antibodies(APA)APA is a big category for all kinds of negative charge phospholipid or lecithin- a protein complex autoantibodies or the same antibody,through its recognition of antigen(target protein) different,and

Myocardial infarction in antiphospholipid antibody syndrome

A 52-year-old man was admitted to hospital with chest pain after physical activity. Emergency coronary angiography showed multiple throm-boembolic occlusions in the anterior descen-ding coronary artery and in the right coronary artery. Further testing revealed anticardiolipin and ?2-glicoprotein antibodies (the patient had been diagnosed for ulcerative colitis and poly-myalgia rheumatica). Heparin and nitrate were administered intravenously in addition to oral aspirin and metoprolol. Soon after, the patient referred a withdrawal of chest oppression, and his general clinical condition rapidly stabilised. A follow-up examination was performed 9 months later the discharge: he had resumed most of his activities and sieric concentration of lupus anticoagulant antibodies and anticardiolipin an- tibodies, IgM isotype, were decreased.

CLINICAL SIGNIFICANCE OF DETECTING SERUM ANTIBODIES TO NUCLEOPROTEIN AND GLYCOPROTEIN G_2 OF HANTAAN VIRUS IN PATIENTS WITH HEMORRHAGIC FEVER WITH RENAL SYNDROME

Antibody blocking enzyme linked immunosorbent assays, respectively detecting antibodies to Hantaan virus nucleoprotein (NPAb) and glycoprotein GZ (G,Ab), were developed using monoclonal antibody L133, L13r3, LV48A and LVZB28B NPAb and GZAb in 291 serum samples from 65 patientswith kemorrkagic fever with renal syudrome (HFRS) were detfrmlned by these methods. The positive rates or NPAb were 90N on day 2-3 and 100 % on day 8-9 arter onset of disease, respectively.NPAb titers Increased during fever period and reached Peak levels during kypotensive and oliguric periods of HFRS. It was suggested that NPAb might be an important component Involved in the immunopathogenlc lin'alrmeut of HFRS and the detection of NPAb might be useful for the early diagnosis or HFRS. The I,osltlve rates and titers of GZAh were very low during the rirst three periods,namely rever, hypoteuslve and ollgurlc periods, and reached high levels during the convalescent period. GRAb titers were negatively related to the I,rotelnurla levels during the course of HFRS. It wasIndicated that GZAb might be the main component or neutralizing autlhodles to Hantaan virus Infection and the efrlclent production or GZAb was a good marker ror predicting the recovery and betterprognosis of HFRS.

Relapse of both small cell lung cancer and Lambert-Eaton myasthenic syndrome after a 13-year disease-free survival period

Lambert-Eaton myasthenic syndrome(LEMS) is a paraneoplastic syndrome and only 3%of small cell lung carcinoma(SCLC) patients have LEMS.Moreover,the recurrence of SCLC after a disease-free survival(DFS) of more than 10 years is rare.We report a patient who had a recurrence of both SCLC and LEMS after a 13-year DFS period.A 69-year-old man was diagnosed with LEMS and SCLC(cT0N2M0,stage ⅢA) 13 years ago.Chemoradiotherapy was performed and a complete response was achieved.With anticancer treatment,the LEMS symptoms was alleviated.At the age of 82 years,gait disturbance appeared followed by left supraclavicular lymphadenopathy and further examination revealed the recurrence of SCLC.Careful screening for the recurrence of SCLC might be needed when the patient has recurrent or secondary paraneoplastic neurological syndrome even after a long DFS period.

Autoimmune polyglandular syndrome type 3 complicated by mineralocorticoid-responsive hyponatremia of the elderly

We experienced the first case with autoimmune polyglandular syndrome type 3(anti-thyroid peroxidase ant ib ody-positive hypothyroidism and anti-glutamic acid decar boxylase antibody-positive diabetes) complicated by miner alocorticoid-responsive hyponatremia of the elderly.This case is also a rare slowly progressive insulin-dependent diabetes mellitus(SPIDDM) case,for which the patient has been treated for many years with sulfonylurea or glinide.Our observation also demonstrated that glucose metabolism in autoimmune diabetes such as SPIDDM is influenced by appetite,thyroid function and glucocorticoid effect.

Antibodies Against Annexin V and Prothrombin,Their Correlation with Other Anti-phospholipid Antibodies in Recurrent Pregnancy Loss

Objective To study the findings of serum antibodies against annexin V, prothrombin, ph-inositol, ph-acid, ph-ethanolamine, ph-serine, ph-glycerol, cardiolipin, and beta2-glycoprotein I and analyze the trophoblast annexin V receptors Methods Sera from 156patients aged 26-41 years with recurrent pregnancy loss （3-7 times） were investigated. Eighty-four fertile healthy women aged 24-38 years were included in a control group. ELISA methods were used for detecting a panel of sera anti-phospholipid antibodies. Immunolocalization of annexin V receptors in 143 trophoblast specimens of 156 patients was investigated by the immunofluorescence technique using Annexin V-FITC, Apoptosis and Annexin V-CY3 commercial kits. Results Positivity for anti-phospholipid antibodies mainly against ph-serine, ph- ethanolamine, and ph-inositol was found together in 80. 8%（126 out of 156 patients）, anti-prothrombin antibodies in 12% （18）, and anti-annexin V antibodies in 13. 5% （21） women. No significant levels of anti-phospholipid antibodies were found in 6 controls. Placenta immunohistopathology also exhibited some changes manifested by the presence of apoptotic and necrotic cells in trophoblast, and very few microthrombotization in some intervillous spaces. Conclusion Our detailed study demonstrated the prevalence of majority of antiphospholipid antibodies as a high risk factor for repeated reproductive failure. Very low microthrombosis in placentas could be explained by the changes of haemocoagulation properties out of uterus.

Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive

Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4+ receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself. Since the CD4+ T cell population is actively involved; the ultimate outcome of human immunodeficiency virus infection is total collapse of the host immune system. Mathematical modeling of the stages in viral membrane protein-host cell receptor-coreceptor interaction and the effect of antibody vaccine on the viral entry into the susceptible host cell has been carried out using as impulsive differential equations. We have studied the effect of antibody vaccination and determined analytically the threshold value of drug dosage and dosing interval for optimum levels of infection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that systematic drug dosage of the immune cells leads to longer and improved lives.