Russian Influenza Research Articles

Pulmonary CD4 + cytokine responses in mice reveal differences in the relative immunogenicity of cold-adapted influenza A vaccine donor strains

We previously described differences in the 50% protective dose and isotype-specific antibody secreting cell (ASC) responses to US and Russian influenza A cold-adapted (ca) donor strains in the lungs of BALB/c mice [Wareing MD, Watson JM, Brooks MJ, Tannock GA. Immunogenic and isotype-specific responses to Russian and US cold-adapted influenza A vaccine donor strains A/Leningrad/134/17/57, A/Leningrad/134/47/57, and A/Ann Arbor/6/60 (H2N2) in mice. J Med Virol 2001;65(1):171–7]. A/Leningrad/134/17/57 (Len/17-ca) was shown to be a superior immunogen to A/Leningrad/134/47/57-ca (Len/47-ca), which, in turn, was superior to A/Ann Arbor/6/60-ca (AA-ca) but no other comparative data exist. In order to extend our findings and determine a means for selecting the most immunogenic ca influenza A vaccine, the intracellular cytokine responses by CD4 + and CD8 + T cells to AA-ca, Len/47-ca and Len/17-ca and their respective wild-type parental viruses were compared in mice. Day 5 after infection with Len/17-ca, when levels of IL-2, -4 and -10 were highest in the mediastinal lymph nodes (MLN) and lungs, was chosen as the optimum time to harvest lymphocytes and 72 h was determined to be the optimum re-stimulation period for lymphocytes by APCs. Under these conditions, the frequency of CD4 + and CD8 + cells expressing cytokines was highest in the lungs compared with the MLN. A dominant IL-6 response was induced, although all virus strains induced a Th1/Th2 cytokine profile. While the CD8 + cytokine response appeared non-specific, the cytokine response elicited in the lungs by CD4 + cells to Len/17-ca-inoculation was greater than that induced by Len/47-ca, or AA/ca. The CD4 + cytokine response in the lungs may be a useful measure of immunogenicity to determine the most effective influenza reassortant for inclusion in vaccines.

Protective efficacy of intranasal cold-adapted influenza A/New Caledonia/20/99 (H1N1) vaccines comprised of egg- or cell culture-derived reassortants

Live, cold-adapted, temperature-sensitive (ca/ts) Russian influenza A vaccines are prepared in eggs by a 6:2 gene reassortment of the ca/ts donor strain A/Leningrad/134/17/57 (H2N2) (Len/17) with a current wild-type (wt) influenza A strain contributing hemagglutinin (HA) and neuraminidase (NA) genes. However, egg-derived reassortant vaccines are potentially more problematic to manufacture in large quantities than vaccines from cell-based procedures. To compare egg- and cell culture-derived reassortant vaccines, we prepared in Madin Darby canine kidney (MDCK) cells two cloned, ca/ts reassortants (25M/1, 39E/2) derived from Len/17 and a wt reference strain A/New Caledonia/20/99 (H1N1) (NC/wt). Both 25M/1 and 39E/2 reassortants preserved the ca/ts phenotype and mutations described for internal genes of the A/Len/17 parent. When compared to a commercial, egg-derived ca/ts Russian A/17/NC/99/145 (H1N1) New Caledonia vaccine (NC/145), the MDCK-derived reassortant 39E/2 vaccine conferred similar levels of protection in ferrets challenged i.n. with 7 × 10 10 pfu of NC/wt. In a dose-ranging study, the protective vaccine dose for 50% of ferrets (PD 50) was less than 1.2 × 10 4 pfu for the 25M/1 vaccine derived by recombination and amplification in MDCK cells. Clonal isolates of ca/ts influenza A/New Caledonia/20/99 (H1N1) obtained by recombination and amplification entirely in MDCK cells can be highly protective i.n. vaccines.

The etiological surveillance for influenza in Russia during the seasons 1993–2003

Influenza A(H1N1), A(H3N2), and B viruses circulated in Russia during 1993–2003. In those years, A(H1N1) viruses caused four epidemics, A(H3N2) viruses caused eight epidemics, and B viruses caused seven epidemics. Strains similar to A/Beijing/262/95 were first isolated in Russia in 1998 and B/Victoria/2/87-like strains in 2003. The study of antigenic and biological properties of epidemic A(H3N2) strains showed their hemagglutinin heterogeneity.

Development and evaluation of live influenza (LIV) cold-adapted reassortant vaccines in cell culture

The Russian influenza A live virus vaccine (LIV) is based on the temperature sensitive ( ts) and cold-adapted ( ca) A/Leningrad/134/17/57 (H2N2) donor strain (Len/17). Reassortants between current circulating A strains and the ca donor strain are traditionally prepared in eggs. MDCK cells have been used for the commercial manufacture of inactivated whole virus influenza vaccines. There has, as yet, been no transition into cell culture for the development of LIV. In this report we have looked at cell-culture derived reassortants with respect to their ability to maintain their phenotypic and genetic characteristics.

An evaluation of the genetic stability and pathogenicity of the Russian cold-adapted influenza A donor strains A/Leningrad/134/17/57 and A/Leningrad/134/47/57 in ferrets

The influenza A components of live attenuated vaccines used in Russia have been prepared as reassortants of the cold-adapted (ca) H2N2 viruses, A/Leningrad/134/17/57-ca (Len/17) and A/Leningrad/134/47/57-ca (Len/47), and virulent epidemic strains. The lesions responsible for attenuation within the six internal genes of each donor strain have been sequenced and described, but relatively little is known as to their stability before and after passage in susceptible hosts. In the work reported in this paper, RT-PCR restriction analysis and limited sequencing of individual genes were used to evaluate the stability of lesions in stocks of the both donor strains after passage in ferrets, which have been used widely as susceptible hosts for assessment of the virulence of influenza strains. Len/47 was shown to possess expected lesions by RT-PCR and restriction analysis. Substitution at position 1066 of the NP gene, which has been previously reported to be unique to Len/47 [Klimov et al., Virology 186 (1992) 795], was also shown to be present in all clones of Len/17. This change was confirmed by limited sequence analysis and was shown to be retained in progeny viruses isolated from the lungs and turbinates of inoculated ferrets. Two other changes in the PB2 and PB1 genes that were present in Len/47 were detected by limited sequence analysis alone. Further previously unreported minor changes were shown to be present for Len/17 and Len/47, but not both, and their significance is unknown. Limited replication of each donor strain occurred in ferrets and minimal clinical signs and histopathology were present. By contrast, the parental strain Len/57 and the recent epidemic strain A/Sydney/6/97 induced clinical signs and histopathology that were typical of influenza disease.

The Russian influenza in the United Kingdom, 1889-1894.

The pandemic of severe influenza known in western Europe as the Russian flu, with its associated infections, caused extensive morbidity and high general mortality. In the United Kingdom, as elsewhere, sufferers and their doctors were hard put to explain the visitatiion and resorted to analogies with physical or bacteriological phenomena, or recalled older beliefs in extra-terrestrial forces. The outcomes were more disturbing than was appreciated at the time, or since. The Russian influenza and its sequelae might well have had a crucial part in creating the 'spirit of the 1890s'.

Origin and evolutionary characteristics of antigenic reassortant influenza A (H1N2) viruses isolated from man in China

During the 1988/1989 influenza season, five antigenic reassortant influenza A (H1N2) viruses not previously isolated from man were isolated in Hebei province, People's Republic of China. All isolates contained haemagglutinins (HAs) and neuraminidases (NAs) which were antigenically similar to those of the recent Russian (H1N1) and Hong Kong influenza A (H3N2) viruses, respectively. The results of antigenic and nucleotide sequence analyses revealed that the genes encoding the polymerase, nucleoprotein, NA, matrix and non-structural proteins of the reassortant A/Hebei/24/89 (H1N2) virus were derived from the H3N2 parent virus, whereas its HA gene was from the H1N1 parent virus. The nucleotide sequences of the HA (encoding the HA1 subunit) and NA genes of the reassortant viruses were also determined. Phylogenetic trees constructed from these data by the neighbour-joining method revealed that the HA gene of the reassortant virus was closely related to those of recent human H1N1 viruses, whereas the NA gene was related to a recent human Hong Kong (H3N2) virus lineage.

Comparison of amantadine and rimantadine for prevention of type A (Russian) influenza

The efficacies of 200 mg daily doses of amantadine and of rimantadine for prevention of infection and illness due to influenza A/USSR/77 (H1N1) virus were compared in a double-blind, placebo-controlled study on a college campus. Frequencies of symptoms that might have been side effects of the drugs were not significantly different from those in placebo recipients. Analyses indicated that the trial was initiated late in the epidemic and that an age-related protective effect against A/USSR virus existed; seroconversion frequencies were 52 139 (37%) among 18–19-year-olds, 33 130 (25%) among 20–21-year-olds, and 5 39 (12.8%) among 22–24-year-olds. Among initially antibody-negative (<1 : 4 in complement fixing and neutralizing tests and <1 : 8 in hemagglutination inhibition tests) 18–19-year-old students, amantadine was associated with significantly fewer seroconversions ( P = 0.01) and both less infection and milder illness than occurred in placebo recipients ( P<0.05). Although rimantadine was not accompanied by reduction in frequency of seroconversions in the same age group, illness frequency and severity among seroconverters were significantly reduced when compared to placebo recipients ( P<0.01). Amantadine and rimantadine appear suitable for use in young adults. Although other studies have suggested greater effectiveness of rimantadine than of amantadine against influenza, no evidence for this was seen in the present study which used both drugs at the same dose.

Russian Influenza in Two University Communities

Abstract The H1N1 influenza A virus (A/USSR/90/77) appeared first in China, then spread to the United States in January 1978, causing significant outbreaks of influenza among younger age groups. Because college students were particularly affected, epidemiologic investigations were done to define the impact of illness on university populations. We describe influenza outbreaks involving two college campuses (the Universities of Michigan and Colorado). At both schools, illness attack rates were significantly higher for students than for older faculty and staff members. At the two respective campuses, 25 and 36% of those ill who were surveyed sought medical care. Bed confinement averaged 3.8 days at one school (Michigan). At the other school (Colorado), ill students missed an average of 2.8 days of class. Influenza A (H1N1) virus was isolated from specimens from acutely ill students at both campuses. These investigations illustrate the practical usefulness of college campuses as sites for monitoring the activ...

Evaluation of influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and cold-adapted recombinant viruses in seronegative adult volunteers.

Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and ca recombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID(50)) for each recombinant was approximately 10(5.0) 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the ca vaccinees given 300 HID(50) and approximately 70% of ca or ts vaccinees who received 10 to 32 HID(50) of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 ts and ca recombinants.

Prevention of Russian Influenza by Amantadine

We tested the effectiveness of amantadine hydrochloride in prevention of illness and infection caused by Russian (h1n1) influenza. The trial lasted seven weeks and was double-blind and placebo controlled. The dosage used was 200 mg daily. Efficacy in prevention of serologically confirmed clinical influenza was 70.7%. Efficacy in prevention of infection, symptomatic or asymptomatic, was 39.4%. Side effects seen were all mild, began within two days of the start of the trial, and terminated rapidly on cessation of prophylaxis. The withdrawal rate attributable to use of amantadine was 6.2%. Those who continued to receive prophylaxis for the remainder of the trial did not exhibit excess side effects. It is concluded that amantadine is safe and effective in prophylaxis of H1N1 strains, as has been shown previously for other subtypes of A influenza.

Prevention of Russian influenza by amantadine

Prevention of Russian influenza by amantadine

Swine influenza vaccine program in the community: acceptability, reactions and responses.

The operation of the national swine influenza immunization program was observed in the community of Tecumseh, Michigan. The purpose was to determine acceptability of a parenteral vaccine intended for the general population. Participation of the residents was excellent. More than 64 per cent of eligibles were vaccinated; this figure resembled that of the rest of the local area, but not the national figures nor a suburban area of Michigan where a similar study was carried out. Sore arm after vaccination was reported most frequently in younger female participants; however, sore arm was accepted as part of the process of vaccination and not considered a reaction by most. Such perceived reactions were not as commonly reported as in the large suburban area. Antibody response to the vaccine was excellent, not only in terms of antibodies to the swine virus itself but also in terms of cross reactive antibodies to the emergent H1N1 (Russian) influenza strain. As a result of the program, many vaccine recipients in the 25 to 49 year age groups are protected against this new epidemic virus.

CEREBRAL SIGNS AND SIMULATIONS IN PNEUMONIA.Read before the Forty-eighth Annual Session Wisconsin State Medical Society.

It is probable that the various papers on the different inflammatory diseases of the lungs, to be presented by this Committee, will take into account the cerebral complications and counterfeits often present, as well as other more frequent, if less serious, complications; and perhaps so fully that anything more would be superfluous. Still, the relative frequency and importance of these cerebral manifestations, grown more frequent and more important since the Russian influenza added its baleful quota to the list of human ills, gives good reason for something of repetition. Indeed, when different writers discuss the subdivisions of lung inflammations practically, that is from the standpoint of bedside observation, there will be much of repetition all through, for at the bedside we find few of those distinct entities which the text-books delight to photograph and catalogue, but instead, a mixture of conditions which baffle rather than invite either delineation or classification.