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PubMed1982

A re-examination of chiasma terminalization and chiasma frequency in male mice.

The distribution and frequency of chiasmata have been analyzed in male BALB/c mice. Bivalents were classified in terms of the number of interstitial chiasmata (CH) and terminal associations (TA) present as follows: 1CH, 2CH, 1TA, 2TA, 1CH X 1TA, 1CH X 2TA, 2CH X 1TA, 2CH X 2TA and 0. We provide evidence that the TA frequently dissociates during 1st meiotic prophase. Consequently six of the observed bivalents may be derived from three basic bivalent types (namely 2CH X 2TA, 1CH X 2TA and 2TA) by dissociation of the TA according to the following schemas: (1) 2CH X 2TA leads to 2CH X 1TA leads to 2CH, (2) 1CH X 2TA leads to 1CH X 1TA leads to 1CH, and (3) 2TA leads to 1TA leads to 0. We also provide evidence that interstitial chiasmata do not move, which implies that a TA can not be formed by chiasma terminalization. The chiasma frequency estimated by assuming that terminal associations do not result from terminalized chiasmata is 17.2+/-2.4 compared to a value of 25.4+/-2.2 calculated on the assumption of chiasma terminalization.

Animals↗
PubMed1991

Chromatin behaviour under influence of puromycin and 6-DMAP at different stages of mouse oocyte maturation.

Preovulatory mouse oocytes were cultured in vitro up to each subsequent stages of maturation: germinal vesicle (GV), germinal vesicle breakdown (GVBD), groups of not yet individualized bivalents, circular bivalents, late prometaphase I, metaphase I, anaphase I and telophase I. The stages were identified in living oocytes by fluorescence microscopy using Hoechst 33342 as a specific vital dye. Oocytes from each stage of development developed in vitro and ovulated metaphase II oocytes were subsequently cultured in the presence of puromycin or 6-dimethylaminopurine (6-DMAP), an inhibitor of protein phosphorylation. The effects on chromatin of these drugs were studied during and at the end of culture by fluorescence and electron microscopy. We found that puromycin and 6-DMAP stop meiosis when applied at all stages of oocyte maturation, except for metaphase II. Oocytes at this stage are activated by puromycin. Reaction of the oocytes to the two drugs is different at GV and at metaphase II. All of the other stages react to the drugs by chromatin compaction, which can be followed by chromatin decondensation to form a nucleus. Our results suggest that late prophase chromatin condensation, bivalent individualization and retention of their individuality, as well as individualization of monovalents from telophase and retention of their individuality at metaphase II, are dependent on protein phosphorylation. The events occurring between metaphase I and telophase I are independent of protein synthesis and phosphorylation. The events occurring between metaphase II and formation of the nucleus are independent of protein synthesis.

Adenine↗
PubMedDate not supplied

Calcium channels in the cell membrane.

The development of the intracellular perfusion technique made isolated nerve cells an extremely convenient object for the detailed study of calcium channels, which allow the corresponding ions to enter the cell through the surface membrane during excitation. A wide range of investigations conducted in this object has shown that calcium channels, allowing the passage of bivalent cations in the order of preference Ba greater than Sr greater than Ca greater than Mg, bind these ions with the aid of a binding group located inside the channel. Other bivalent cations (Co, Ni, Mn, Cd), which bind too strongly with this group, become competitive channel blockers. In the absence of bivalent cations in the extracellular medium the calcium channels lose their selectivity and begin to transmit monovalent cations effectively; the reason for this transformation is detachment of the bound calcium ions from a special regulating group at the mouth of the calcium channels. Calcium channels can exist in two functional states: conducting and nonconducting. The transition between these states is accompanied by movement of charges inside the membrane ("gating currents"). The statistical kinetics of this transition, like the kinetics of gating currents, can be described by a modified Hodgkin-Huxley equation, with an activation variable raised to the power of 2. During long-term membrane depolarization the calcium channels pass into an inactivated state, which is connected with the recurrent blocking action of calcium ions, entering the cell, on the channels. Meanwhile, for some types of calcium channels, potential-dependent activation analogous to that in sodium or potassium channels is observed.

Animals↗
PubMed1977

Ion permeability and strength of cell contacts: ion permeability and mechanical properties of cell contacts in small intestine epithelium.

The effects of several simple parameters (pH, concentration of bivalent cations, osmotic pressure, and temperature) on the ion permeability and mechanical properties of cell contacts have been investigated. It has been shown that the mechanical properties of a cell contact make it possible to describe it as a viscoelastic system. The main contribution to cell adhesion is made by the tight junction. Two populations of acidic centers have been identified on the cell membrane surface. One population interacts with bivalent cations to assure cell adhesion. The other population of weaker acidic centers regulating ion permeation is involved in the cell membrane's interaction of the repulsion type. An intimate correlation has been established between changes in passive transepithelial ion permeability and cell adhesion in response to changes in pH and in bivalent cation concentration. Such a correlation is possible if the tight junction is the principal contributor to the passive ion permeability and mechanical strength of the cell contacts.

Animals↗
PubMed2005

Comparison of IgG and F(ab')2 fragments of bispecific anti-RCCxanti-DTIn-1 antibody for pretargeting purposes.

PURPOSE: An effective pretargeting strategy was developed for renal cell carcinoma (RCC) based on a biologically produced bispecific monoclonal antibody: anti-RCCxanti-DTPA(In) (bsMAb: G250xDTIn-1). Tumour uptake of a (111)In-labelled bivalent peptide after pretargeting with bsMAb G250xDTIn-1 was relatively high compared with that in other pretargeting systems using chemically coupled F(ab')(2) fragments. Here, we investigated the effect of the bsMAb form in the pretargeting strategy. METHODS: To determine the optimal interval between the administration of each of the bsMAb forms and the (111)In-labelled bivalent peptide, the biodistribution of the radioiodinated bsMAb forms was studied in athymic mice with subcutaneous SK-RC-1 RCC tumours. Since tumour targeting of the radiolabelled peptide depends on the bsMAb form and dose, a bsMAb dose escalation study was carried out for both bsMAb forms. Under optimised conditions, the biodistribution of the (111)In label in mice with pretargeted RCC was determined from 4 h up to 7 days p.i. RESULTS: The optimal interval between the two administrations was 72 h for the bsMAb IgG and 4 h for the bsMAb F(ab')(2). The optimal bsMAb dose for intact IgG was 67 pmol and the optimal bsMAb F(ab')(2) dose was 200 pmol. Targeting of the pretargeted RCC with 4 pmol (111)In-labelled bivalent peptide revealed high tumour uptake with both bsMAb forms. CONCLUSION: With the pretargeting strategy, using either bsMAb IgG or bsMAb F(ab')(2), very efficient peptide targeting of the tumour was obtained. Uptake and retention of the radiolabel in the tumour with the pretargeting approach are not affected by the bsMAb form used.

Animals↗
PubMed1997

Lampbrush chromosomes and chiasmata of sex-reversed crested newts.

Triturus cristatus carnifex provides a particularly clear example of sexual dimorphism for chiasma frequency and localisation. Oocytes from normal XX females routinely carry one proximal chiasma on each arm of their lampbrush bivalents. Spermatocytes from normal XY males have more numerous and relatively distal chiasmata. Lampbrush chromosomes from the oocytes of sex-reversed XY neofemales are found to resemble those from normal oocytes in having one proximal chiasma on each bivalent arm. A comparison of particular markers on the heteromorphic long arm of chromosome 1 provides evidence to equate the lampbrush 1A to somatic 1A, and confirms previous reports that lampbrush chromosome 1A is slightly longer than 1B. The XY sex bivalent of neofemales does not show any obvious heteromorphy of recognised marker loops.

Animals↗
PubMed2000

Distribution of Atr protein in primary spermatocytes of a mouse chromosomal mutant: a comparison of preparation techniques.

In this study, we examined the suitability of a three dimensional preparation technique for studying chromosome behaviour in the first meiotic prophase in the mouse chromosomal mutant T(1;13)H/T(1;13)Wa. To preserve cellular shape, primary spermatocytes were encapsulated in a fibrin clot. Conventionally sedimented prophase nuclei served as controls. Axial elements and lateral synaptonemal complex components were subsequently stained by immunofluorescence and the presence of axial elements at the pachytene stage was highlighted with indirect immunofluorescence against the Atr protein. We compared the distribution of Atr signal in the fibrin-embedded spermatocytes with surface-spread preparations and immunohistochemically stained histological sections of seminiferous tubules. Furthermore, fluorescence in situ hybridisation of the mouse minor satellite DNA was done on fibrin-embedded spermatocytes. The Atr signal is most conspicuous in fibrin-embedded nuclei on unpaired axial elements during pachytene, both for sex chromosomal and for autosomal segments, and expanding from these elements into the surrounding chromatin. Both spread and encapsulated zygotene nuclei with extended axial element formation proved to be positive for Atr. Mid- to late zygotene nuclei were devoid of 3,3'-diaminodibenzene deposition in the histological sections. Highlighting the unpaired axial elements in the small heteromorphic 1(13)H;1(13)Wa bivalent with an Atr signal enabled meiotic analysis of this bivalent to be carried out in a three-dimensional context. Thus, proximity of this bivalent with the sex chromosomes is found more often in three-dimensional preparations than in spread preparations. Furthermore, the development of the Atr signal over the sex chromosomes as pachytene proceeds helps in substaging of this long and heterogeneous meiotic phase, in sedimented but especially in fibrin-encapsulated nuclei.

Animals↗
PubMed2005

Cohesion proteins are present in centromere protein bodies associated with avian lampbrush chromosomes.

Proteins of sister chromatid cohesion are important for maintenance of meiotic chromosome structure and retention of homologous chromosomes in bivalents during diplotene. Localization of the cohesion proteins within nuclei of growing oocytes merits special attention, particularly in avian oocytes, in which diplotene chromosomes assume the form of lampbrush chromosomes (LBCs). We performed indirect immunostaining using antibodies against cohesins SMC1alpha, SMC1beta, SMC3, Rad21, and the SA/STAG family on chaffinch, pigeon and duck LBCs spreads, and frozen ovary sections. On LBCs spreads, antibodies to the majority of cohesins showed punctate staining on chromosome axes. LBC lateral loops, where sister chromatids are separated, did not show cohesin components. The spherical entities attached to the LBCs centromeres in avian germinal vesicles, the so-called protein bodies (PBs), were enriched in SMC1alpha, SMC3, Rad21, STAG1 and STAG2. The synaptonemal complex component SYCP3, which also participates in cohesion, was detected in the axes of avian lampbrush bivalents and, to a greater degree, in the PBs. In vitellogenic oocytes, cohesion proteins persist in the PBs associated with condensing bivalents when they concentrate into the karyosphere. These results indicate that cohesion proteins accumulate in centromere PBs in avian oocytes and are involved into structural maintenance of lampbrush chromosome axes.

Animals↗
PubMed1989

Anion transport through the contraluminal cell membrane of renal proximal tubule. The influence of hydrophobicity and molecular charge distribution on the inhibitory activity of organic anions.

Three different mechanisms of anion transport have been identified for the contraluminal membrane in the proximal tubule of the rat kidney. These mechanisms are specific for the transport of sulfate, dicarboxylate and p-aminohippurate anions. Sulfate transport is inhibited by bivalent organic anions with a distance between the charges of less than 7 A. The sulfate system acts in two modes: in a planar mode for anions with flat charged residues such as COO- and a charge separation of 3-4 A or in a bulky mode for groups such as SO3H- and a charge separation of 4-7 A. Monovalent anions can be accepted if there is a hydrophobic core next to the negative charges. Dicarboxylate transport is inhibited exclusively by anions with two charge centers located within 5 to 9 A, one of those possibly being a partial charge of -0.5 elementary charges. p-Aminohippurate transport is inhibited by monovalent anions, if these have a hydrophobic domain with a minimal length of about 4 A. Bivalent anions inhibit, if they have a charge distance of 6-10 A; both charges can be partial charges of about -0.5 elementary charges. Longer bivalent anions can be effective provided they have a sufficiently large hydrophobic domain. For the sulfate and p-aminohippurate systems it is found that anions with high acidity yield good inhibition. The overlapping specificities of the three systems with respect to charge distance and hydrophobicity allow them to accept a large variety of organic anions.

Algorithms↗
PubMed1994

Chemical synthesis of bispecific monoclonal antibodies: potential advantages in immunoassay systems.

To date, the applications of bispecific antibodies in immunoassay and immunocytochemical procedures have been directed at uniting two different biomolecules through the binding of epitopes on each respective substance. In this study, bispecific antibodies were constructed in which both binding sites were directed to two different epitopes of the same target molecule. Two types of bispecific antibody were constructed; a bivalent bispecific monoclonal antibody and multivalent bispecific polymers. The binding characteristics of each were investigated for changes in specificity and binding strength relative to 1:1 mixtures of parent antibodies. A bivalent bispecific antibody (BBA) was synthesised by the method of Glennie et al. (1985) from monoclonal antibodies recognising the 'M' or 'B' units of creatine kinase (CKMB). The BBA had enhanced specificity for CKMB with diminished recognition of CKMM and CKBB. A less tedious method of producing bispecific antibody involving heterobifunctional cross-linkage was used to produce multivalent bispecific antibodies (MBAs). Certain MBAs constructed to bind 'M' and 'B' units of CKMB demonstrated enhanced specificity and affinity for CKMB. MBAs were also produced to opposite ends of the 39 amino acid peptide adrenocorticotrophic hormone (ACTH). One of these demonstrated an enhanced affinity of 41-fold. We conclude that while conventional synthesis of bispecific bivalent antibodies is not a practical proposition for immunoassay development, antibodies with similar advantages can be produced with a simple method using the heterobifunctional cross-linker. The production of certain bispecific antibody combinations appears to enhance the formation of antibody-antigen matrices conferring higher binding affinities than can be achieved with an antibody mixture alone.

Adrenocorticotropic Hormone↗
PubMed1984

A general treatment of chromosome synapsis in even-numbered polyploids.

Relationships between frequencies of fully paired pachytene configurations are examined for even-numbered polyploids, up to decaploids and beyond. Sequential association is assumed at any given number of equidistant synaptic sites showing uniform propensities for partner exchange. Only with two sites per chromosome, can each configuration represent an equal proportion of the nucleus. In the limit as the number of sites tends to infinity and the intervals between them tend to zero, pachytene multivalent frequency is seen to be a function of bivalent frequency, the minimum number of changes in pairing partner and ploidy. Each type of multivalent may represent the entire nucleus only in the lowest ploidy which can support it, thereafter becoming rare. Sets of homologous multivalents are never likely to be common and large multivalents are expected to be scarce, unless representing maximal configurations. Only bivalents can prevail at every even-numbered ploidy level. At constant bivalent frequency, the transition from discrete to continuous pairing favours the largest type of multivalent. These deductions provide a basis for investigations of the mechanics of chromosome synapsis and may lead to a comprehensive theory of genome analysis.

Cell Nucleus↗
PubMed1985

Increased affinity of dimeric enkephalins is not dependent on receptor density.

The equilibrium binding and dissociation kinetics of the enkephalin dimer bis-(D-Ala2-D-Leu5-enkephalin)-ethylenediamide (designated DPE2) to neuroblastoma glioma NG108-15 cells were investigated and compared with the monomers D-Ala2-D-Leu5-enkephalin (DADL) and D-Ala2-Leu5-enkephalinamide (DALEA). Binding was studied after exposure of the membrane to increasing concentrations of the irreversible delta receptor selective ligand FIT in order to decrease the density of binding sites on the cell membrane. The increased affinity of DPE2 did not revert to that of the monomer DADL by this reduction of binding sites. Similarly, the dissociation of DPE2 did not approach that of the monomer DALEA in the presence of 1 microM DALEA. These data strongly suggest that crosslinking does not occur, and fail to confirm the hypothesis that dimers with short spanning chain length aid the clustering of receptors. We postulate: 1) If the dimer binds to a bivalent binding site, the monovalent binding state of our bivalent ligand may not exist to an appreciable extent, and 2) the bivalent ligand cannot bind when the binding site is irreversibly blocked by a monovalent ligand.

Animals↗
PubMed1990

Polyvalent interaction of antibodies with bacterial cells.

We have studied the physical-chemical characteristics of the interaction of peroxidase-labelled rabbit antibodies with Bacillus sp. bacterial cells. The antibodies are able to bind bivalently with two antigen sites on the bacterial cells with the formation of intramolecular "cyclic" complexes. A kinetic model is proposed suggesting the existence of monovalent and bivalent cell surface antigens. The equilibrium constant of the bivalent IgG binding to the bacterial cell is by two orders of magnitude higher as compared to monovalent Fab fragments. The intramolecular reaction between the free active site of the monovalently bound antibody and a free antigen site on the cell surface is the rate limiting step of the polyvalent interaction. Formation of the cyclic complexes seems to be accompanied by essential tension of bonds and deformation of the IgG molecule. Agglutination of bacterial cells was also studied. The cell agglomerate size dependence on the antibody concn has a threshold. Agglutination proceeds under conditions where the antigen-antibody binding on the cell surface is far from equilibrium.

Agglutination↗
PubMed1992

Some kinetic properties of pyruvate kinase from Trypanosoma brucei.

We have studied the kinetics of the allosteric interactions of pyruvate kinase from Trypanosoma brucei. The kinetics for phosphoenolpyruvate depended strongly on the nature of the bivalent metal ions. Pyruvate kinase activated by Mg2+ had the highest catalytic activity, but also the highest S0.5 for phosphoenolpyruvate, while the opposite was true for pyruvate kinase activated by Mn2+. The reaction rates of Mg(2+)-pyruvate kinase and Mn(2+)-pyruvate kinase were clearly allosteric with respect to phosphoenolpyruvate, while the kinetics with Co(2+)-pyruvate kinase were hyperbolic. However, Co(2+)-pyruvate kinase was still sensitive to heterotropic activation. Trypanosomal pyruvate kinase is unique in that the best activator was fructose 2,6-bisphosphate. Ribulose 1,5-bisphosphate and 5-phosphorylribose 1-pyrophosphate were also strong heterotropic activators, which were much more effective than fructose 1,6-bisphosphate and glucose 1,6-bisphosphate. In the presence of the heterotropic activators, the sigmoidal kinetics with respect to phosphoenolpyruvate and the bivalent metal ions were modified as were the concentrations of phosphoenolpyruvate and the bivalent metal ions needed to attain the maximal activity. Maximal activities were not significantly changed with Mg2+ and Mn2+ as the activating metal ions. Moreover, with Co2+ and fructose 2,6-bisphosphate or ribulose 1,5-bisphosphate or 5-phosphorylribose 1-pyrophosphate, the maximal activity was significantly reduced. Ribulose 1,5-bisphosphate and 5-phosphorylribose 1-pyrophosphate resembled fructose 2,6-bisphosphate rather than fructose 1,6-bisphosphate and glucose 1,6-bisphosphate in their action in that the K0.5 values for the former 3 compounds increased when Mg2+ was replaced by Co2+, while the K0.5 for fructose 1,6-bisphosphate and glucose 1,6-bisphosphate increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Allosteric Regulation↗
PubMed2004

Specificity of neomycin analogues bound to the packaging region of human immunodeficiency virus type 1 RNA.

The packaging region of HIV-1 RNA contains a number of structural features which are important in the life cycle of the virus, making this segment of RNA a potential target for new types of AIDS-directed drugs. We studied the binding of three neomycin analogues (neo-guanidino, neo-acridine, and neo-neo) to a 171-mer RNA molecule from the packaging region of HIV-1 using quantitative footprinting and circular dichroism. Neo-guanidino produced footprinting patterns and effects on the CD similar to those observed for neomycin and paromomycin, indicating that all three compounds bind to the same regions of the 171-mer. Neo-guanidino binds to SL 1 where it joins the large internal loop, near a bulge in the stem of SL 1, and on SL 2. Neo-acridine, which has an acridine attached to neomycin, and neo-neo, which has two neomycins linked by a flexible tether, bind bivalently, and give very different footprinting and CD results from the other compounds. The neomycin portion of neo-acridine binds to the same sites as neomycin, while the attached acridine group appears to bind to a duplex region in the main stem of the folded 171-mer. Since the footprinting data for this analogue show few enhancements, bivalent binding of neo-acridine appears to stabilize the folded structure of RNA by effectively 'stapling' parts of the structure together. Neo-neo induces significant structural changes in RNA where neomycin binds. This may be related to the inability of both neomycins of neo-neo it find optimal binding sites adjacent to one another without changing RNA structure. The intensity of a strong negative CD band in the spectrum of psi-RNA at 208 nm is sensitive to drug-induced changes in RNA structure. Neo-guanidino and neo-neo (also neomycin and paromomycin), which change RNA structure, cause an increase in intensity while neo-acridine, which induces little distortion to RNA, causes a decrease in intensity. Molecular modeling analysis shows that C-5' of ribose of neo-acridine and neo-neo must be directed away from the binding pocket when these analogues are bivalently bound to RNA. This study showed how variations in the structure of aminoglycosides lead to different binding specificity to part of the packaging region of HIV-1. Such knowledge will be important in design of drugs to target this region.

Base Sequence↗
PubMed2006

Preparation and characterization of monovalent cation selective sulfonated poly(ether ether ketone) and poly(ether sulfone) composite membranes.

Highly charged cation permeable composite membranes were prepared by blending of sulfonated poly(ether sulfone) (SPES) with sulfonated poly(ether ether ketone) (SPEEK) in 0 to 90% weight ratio, to adjust the hydrophobic properties and ion selective nature. Extent of sulfonation was confirmed by 1H NMR and ion exchange capacity and degree of sulfonation depending on blending composition. These membranes were characterized as a function of weight fraction of SPEEK by recording ion-exchange capacity, water uptake, thermogravimetric analysis, membrane conductivity and membrane potential in equilibration with different electrolytic solutions. Membrane permselectivity and solute flux were estimated using these data on the basis of non-equilibrium thermodynamic principles and for observing the selectivity of different membranes for mono- or bivalent counter-ions. It was observed that relative selectivity for monovalent in comparison to bivalent counter-ions were increased with the decrease in SPEEK content in the composite membrane matrix. The range of SPEEK content in the blend from 60 to 80% appears the most suitable for the selective separation of monovalent ions from bivalent ions. Furthermore, highly charged nature and stabilities of these membranes extend their applications for the electro-assisted separations of similarly charged ions as well as other electro-membrane processes.

Journal Article↗
PubMed2006

The role of extracellular calcium in exo- and endocytosis of synaptic vesicles at the frog motor nerve terminals.

In the present study we combined FM 1-43 imaging and electrophysiological recording of miniature end-plate currents (MEPCs) to determine the role of extracellular calcium in synaptic vesicle exo- and endocytosis at the frog motor nerve terminals. We replaced extracellular Ca2+ ions with other bivalent cations (Sr2+, Ba2+, Cd2+, Mg2+) or used a calcium-free solution and monitored fluorescent staining of the nerve terminals in the presence of caffeine, which promotes the release of Ca2+ from intracellular stores. Caffeine has induced FM1-43 internalization only in the presence of bivalent cations in the external solution. The exposure of the neuromuscular junction to caffeine in a calcium-free solution caused a reversible failure of FM 1-43 loading and an increase in the nerve terminal width. This effect of a calcium-free solution was not due to a decrease in exocytosis, because caffeine-induced FM1-43 unloading from the previously loaded nerve terminals, as well as a degree of the MEPCs frequency increase, was unchanged. We conclude that the presence of Ca2+ or other bivalent cations in extracellular space is necessary for endocytosis but not for exocytosis of synaptic vesicles, while transmitter release is promoted by efflux of Ca2+ from intracellular stores. The effect of extracellular Ca2+ on endocytosis might be driven by the non-specific interactions with membrane lipids.

Animals↗
PubMed2006

The immune response and maternal antibody interference to a heterologous H1N1 swine influenza virus infection following vaccination.

This study investigated the efficacy of a bivalent swine influenza virus (SIV) vaccine in piglets challenged with a heterologous H1N1 SIV isolate. The ability of maternally derived antibodies (MDA) to provide protection against a heterologous challenge and the impact MDA have on vaccine efficacy were also evaluated. Forty-eight MDA(+) pigs and 48 MDA(-) pigs were assigned to 8 different groups. Vaccinated pigs received two doses of a bivalent SIV vaccine at 3 and 5 weeks of age. The infected pigs were challenged at 7 weeks of age with an H1N1 SIV strain heterologous to the H1N1 vaccine strain. Clinical signs, rectal temperature, macroscopic and microscopic lesions, virus excretion, serum and local antibody responses, and influenza-specific T-cell responses were measured. The bivalent SIV vaccine induced a high serum hemagglutination-inhibition (HI) antibody titer against the vaccine virus, but antibodies cross-reacted at a lower level to the challenge virus. This study determined that low serum HI antibodies to a challenge virus induced by vaccination with a heterologous virus provided protection demonstrated by clinical protection and reduced pneumonia and viral excretion. The vaccine was able to prime the local SIV-specific antibody response in the lower respiratory tract as well as inducing a systemic SIV-specific memory T-cell response. MDA alone were capable of suppressing fever subsequent to infection, but other parameters showed reduced protection against infection compared to vaccination. The presence of MDA at vaccination negatively impacted vaccine efficacy as fever and clinical signs were prolonged, and unexpectedly, SIV-induced pneumonia was increased compared to pigs vaccinated in the absence of MDA. MDA also suppressed the serum antibody response and the induction of SIV-specific memory T-cells following vaccination. The results of this study question the effectiveness of the current practice of generating increased MDA levels through sow vaccination in protecting piglets against disease.

Animals↗