EFFECT OF TRIVALENT ORAL POLIOVIRUS VACCINE IN AN INSTITUTIONALIZED POPULATION WITH VARYING NATURAL AND ACQUIRED IMMUNITY TO POLIOMYELITIS

PEDIATRICS ◽  
1965 ◽  
Vol 35 (2) ◽  
pp. 236-246
Author(s):  
Martha L. Lepow ◽  
David A. Spence

Ninety-one children in an orphanage, who had varying degrees of natural and acquired immunity to polioviruses, were given three doses of a trivalent poliovirus vaccine at monthly intervals. It was found that among children who lacked protection to one or two types, a single dose of trivalent vaccine resulted in seroconversion to that type. For those who had antibody levels of less than four to all three types, the type 1 component of the vaccine appeared to be less effective than the other two types. An elevation in serum antibody titer was noted more frequently in children who had preimmunization titers of 1:64 or less than in those with high preimmunization titers. Although the mechanism of acquisition of prior immunity was unknown, it must be assumed that many of the subjects had had natural poliovirus infection in the past.

2021 ◽  
Vol 12 ◽  
Author(s):  
Brian D. Aevermann ◽  
Casey P. Shannon ◽  
Mark Novotny ◽  
Rym Ben-Othman ◽  
Bing Cai ◽  
...  

Vaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests that a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine and that a wide range of antibody levels were elicited after three doses. The immune mechanisms responsible for this vaccine response variability is unclear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) correlated with the immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. To explore this correlation further, genes expressed in these mDC subsets were used for feature selection prior to the construction of predictive models using supervised canonical correlation machine learning. The resulting models showed an improved correlation with serum antibody titers in response to full vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype” at pre-vaccination baseline, could dictate response to vaccination.


2021 ◽  
Author(s):  
Brian Aevermann ◽  
Casey P. Shannon ◽  
Mark Novotny ◽  
Rym Ben-Othman ◽  
Bing Cai ◽  
...  

AbstractVaccination to prevent infectious disease is one of the most successful public health interventions ever developed. And yet, variability in individual vaccine effectiveness suggests a better mechanistic understanding of vaccine-induced immune responses could improve vaccine design and efficacy. We have previously shown that protective antibody levels could be elicited in a subset of recipients with only a single dose of the hepatitis B virus (HBV) vaccine. Why some, but not all, recipients responded in this way was not clear. Using single cell RNA sequencing of sorted innate immune cell subsets, we identified two distinct myeloid dendritic cell subsets (NDRG1-expressing mDC2 and CDKN1C-expressing mDC4), the ratio of which at baseline (pre-vaccination) predicted immune response to a single dose of HBV vaccine. Our results suggest that the participants in our vaccine study were in one of two different dendritic cell dispositional states at baseline – an NDRG2-mDC2 state in which the vaccine elicited an antibody response after a single immunization or a CDKN1C-mDC4 state in which the vaccine required two or three doses for induction of antibody responses. Genes expressed in these mDC subsets were used as an approach for feature selection prior to the construction of a predictive model using supervised canonical correlation machine learning. The resulting model showed an improved ability to predict serum antibody titers in response to vaccination. Taken together, these results suggest that the propensity of circulating dendritic cells toward either activation or suppression, their “dispositional endotype”, could dictate response to vaccination. The fact that these mDCs could be modulated via TLR stimulation could guide progress towards design of effective single dose vaccination strategies.


1978 ◽  
Vol 148 (1) ◽  
pp. 148-168 ◽  
Author(s):  
DA Rowley ◽  
GW Miller ◽  
I Lorbach

Complementary antibodies, i.e. antibodies having combining site structures which are at least partially directed against each other, were induced in A/He mice by immunization with phosphorylcholine (Pc) coupled to keyhole limpet hemocyanin or with the Pc-binding IgA myeloma protein, HOPC-8 (H8). Both responses were monitored by enumerating plaque-forming cells and assaying serum antibody levels to Pc and H8. Prior immunization with H8 markedly suppressed subsequent immunization with Pc and vice versa; neither plaque-forming cell response was diminished, however, when mice were immunized simultaneously with Pc and H8. Experiments were designed to determine if the absence of reciprocal regulation was due to change in idiotypes. This was determined by measuring inhibition of plaque formation using complementary antibody. Plaque formation by cells was equally inhibited by high dilutions of the appropriate complementary antibody whether cells were from mice immunized with one, the other, or both antigens. Thus, the absence of regulation could not be accounted for by emergence of different idiotypes. Interestingly, sera from mice immunized to have high responses to both antigens were relatively ineffective in inhibiting plaque formation or suppressing immunization to Pc. However, such sera contained complexes of the complementary antibodies; apparently antibody to Pc in such sera quenches or neutralizes the activity of anti-H8 antibody. But the formation of complexes, at least measurable levels of circulating complexes, must be a result rather than the cause for the absence of reciprocal regulation, since regulation was also absent when immunization to Pc was manipulated so that responses were too low to result in detectable levels of circulating antibody to Pc. It is proposed that simultaneous complementary responses may occur in nature to other antigens and antibodies, and that such simultaneous responses may cause pathologic changes.


2003 ◽  
Vol 71 (4) ◽  
pp. 2239-2243 ◽  
Author(s):  
F. Chris Minion ◽  
Sreekumar A. Menon ◽  
Gregory G. Mahairas ◽  
M. J. Wannemuehler

ABSTRACT The Mycobacterium tuberculosis protein ESAT-6 has unusual immune stimulating activities, has been implicated in the recall of long-lived immunity, and induces protection against tuberculosis in mice. For many diseases caused by bacterial or viral pathogens, a strong cell-mediated immune (i.e., type 1) response is often required for recovery or protection. Therefore, it is important to design immunization regimens that induce agent-specific type 1 immunity. We have shown in previous studies that ESAT-6 could enhance antigen-specific type 1 immune responses in BALB/c mice against a second antigen when presented as a purified fusion protein. It was also of interest to determine if ESAT-6 could enhance the type 1 response against a second antigen beyond that afforded by DNA vaccination through CpG motifs. This was tested by using gene fusions of ESAT-6 and the Mycoplasma hyopneumoniae surface antigen P71. Modified P71 gene sequences were cloned with or without ESAT-6 sequences into a DNA vaccine vector and were used to immunize mice. Splenic lymphocytes from vaccinated mice were tested for gamma interferon (IFN-γ) and interleukin-10 (IL-10) secretion. Serum antibodies were examined for P71 antigen-specific isotype responses. When stimulated in vitro with purified P71 antigen, splenocytes from the ESAT-6:P71 vaccinates secreted higher levels of IFN-γ and lower levels of IL-10 compared to those of vaccinates receiving the P71 construct alone. Furthermore, the immunoglobulin G2a serum antibody levels were significantly higher in the ESAT-6:P71 vaccinates compared to those of the vaccinates receiving P71 alone. In conclusion, ESAT-6 was shown to enhance antigen-specific type 1 immune responses in BALB/c mice when used in DNA vaccines.


Author(s):  
K. T. Tokuyasu

During the past investigations of immunoferritin localization of intracellular antigens in ultrathin frozen sections, we found that the degree of negative staining required to delineate u1trastructural details was often too dense for the recognition of ferritin particles. The quality of positive staining of ultrathin frozen sections, on the other hand, has generally been far inferior to that attainable in conventional plastic embedded sections, particularly in the definition of membranes. As we discussed before, a main cause of this difficulty seemed to be the vulnerability of frozen sections to the damaging effects of air-water surface tension at the time of drying of the sections.Indeed, we found that the quality of positive staining is greatly improved when positively stained frozen sections are protected against the effects of surface tension by embedding them in thin layers of mechanically stable materials at the time of drying (unpublished).


Author(s):  
Prakash Rao

Image shifts in out-of-focus dark field images have been used in the past to determine, for example, epitaxial relationships in thin films. A recent extension of the use of dark field image shifts has been to out-of-focus images in conjunction with stereoviewing to produce an artificial stereo image effect. The technique, called through-focus dark field electron microscopy or 2-1/2D microscopy, basically involves obtaining two beam-tilted dark field images such that one is slightly over-focus and the other slightly under-focus, followed by examination of the two images through a conventional stereoviewer. The elevation differences so produced are usually unrelated to object positions in the thin foil and no specimen tilting is required.In order to produce this artificial stereo effect for the purpose of phase separation and identification, it is first necessary to select a region of the diffraction pattern containing more than just one discrete spot, with the objective aperture.


1972 ◽  
Vol 70 (3) ◽  
pp. 582-590
Author(s):  
B. K. Davis ◽  
I. Noske ◽  
M. C. Chang

ABSTRACT Ethinyloestradiol (EO) fed for various periods before mating to female hamsters affected the timing of mating and pregnancy rate. Slight effects on ovulation, foetal-crown rump length and resorption may have occurred, but effects on implantation were not apparent among pregnant hamsters. The response observed depended upon the feeding schedule adopted: hamsters fed 2.5 mg EO in a single dose, on day 3 before mating, mated normally but had a significantly lower pregnancy rate; on the other hand, animals fed 2.5 mg EO (0.21 mg/day) over three oestrous cycles, days 14–3 before mating, showed variations in the time of mating but had an essentially normal pregnancy rate; and, a group of hamsters who received the same total amount of EO (0.63 mg/day) over one oestrous cycle, days 6–3 premating, showed untowards effects by the steroid on both the timing of mating and pregnancy rate. The implications of these results are considered in relation to fertility control.


2010 ◽  
Vol 51 (1-2) ◽  
pp. 215-224
Author(s):  
Alexander Carpenter

This paper explores Arnold Schoenberg’s curious ambivalence towards Haydn. Schoenberg recognized Haydn as an important figure in the German serious music tradition, but never closely examined or clearly articulated Haydn’s influence and import on his own musical style and ethos, as he did with many other major composers. This paper argues that Schoenberg failed to explicitly recognize Haydn as a major influence because he saw Haydn as he saw himself, namely as a somewhat ungainly, paradoxical figure, with one foot in the past and one in the future. In his voluminous writings on music, Haydn is mentioned by Schoenberg far less frequently than Bach, Mozart, or Beethoven, and his music appears rarely as examples in Schoenberg’s theoretical texts. When Schoenberg does talk about Haydn’s music, he invokes — with tacit negativity — its accessibility, counterpoising it with more recondite music, such as Beethoven’s, or his own. On the other hand, Schoenberg also praises Haydn for his complex, irregular phrasing and harmonic exploration. Haydn thus appears in Schoenberg’s writings as a figure invested with ambivalence: a key member of the First Viennese triumvirate, but at the same time he is curiously phantasmal, and is accorded a peripheral place in Schoenberg’s version of the canon and his own musical genealogy.


2018 ◽  
Vol 47 (2) ◽  
Author(s):  
Kempe Ronald Hope

Countries with positive per capita real growth are characterised by positive national savings—including government savings, increases in government investment, and strong increases in private savings and investment. On the other hand, countries with negative per capita real growth tend to be characterised by declines in savings and investment. During the past several decades, Kenya’s emerging economy has undergone many changes and economic performance has been epitomised by periods of stability, decline, or unevenness. This article discusses and analyses the record of economic performance and public finance in Kenya during the period 1960‒2010, as well as policies and other factors that have influenced that record in this emerging economy. 


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