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Biomedical subjects

B R Murphy

Publications and source records attributed to B R Murphy.

At least 127 records · Page 7Linked to original sources
PubMed1992

Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia--RSV recombinants or RSV.

In studies conducted in the 1960s, children previously immunized with a formalin-inactivated respiratory syncytial virus (RSV) vaccine (FI-RSV) developed a greater incidence and severity of pulmonary disease during subsequent natural RSV infection than did controls. It was previously shown that cotton rats immunized with FI-RSV or immunoaffinity-purified fusion (F) glycoprotein developed enhanced pulmonary histopathology following intranasal challenge with RSV. In the present studies, various forms of immunization, including parenteral inoculation of an immunoaffinity-purified F glycoprotein or a chimeric FG glycoprotein produced in insect cells using a baculovirus vector (Bac-FG), intradermal infection with a vaccinia-F recombinant (Vac-F) or intranasal infection with an adenovirus-F recombinant (Ad-F) or RSV, were compared for immunogenicity, efficacy and ability to alter the host so that enhanced pulmonary histopathology developed during RSV infection 3 months after immunization. Immunization of cotton rats with F glycoprotein, Bac-FG, Vac-F, Ad-F or infection with RSV induced high levels of ELISA-F antibodies, but the antibodies induced by purified F glycoprotein of Bac-FG had low levels of neutralizing activity. Immunization with Vac-F or Ad-F, or infection with RSV induced a high level of resistance to pulmonary RSV replication, whereas animals immunized with Bac-FG or FI-RSV were only partially protected. Following RSV challenge, animals immunized with purified F glycoprotein or Bac-FG developed the highest levels of bronchiolar and alveolar histopathology, those immunized with FI-RSV had intermediate levels, and those immunized with Vac-F or RSV had histopathology scores at control levels. Ad-F immunized animals had elevated scores of bronchiolar but not alveolar histopathology; however, this finding was not reproducible. Passive transfer of pooled immune sera from animals infected with RSV or Vac-F and Vac-G was highly protective, whereas pooled sera from animals immunized with Bac-FG failed to protect the lungs against RSV challenge. Increased pulmonary histopathology was not observed in the passively immunized animals following RSV challenge, suggesting that the histopathology was mediated by RSV-specific T cells. These data indicate that subunit F glycoprotein or chimeric FG vaccines share with FI-RSV the properties of (i) induction of F antibodies with low neutralizing activity and (ii) enhancement of pulmonary histopathology during subsequent RSV infection. These observations confirm the need for caution in studies involving the administration of RSV subunit vaccines to seronegative humans.

Animals↗
PubMed1992

Immunogenicity of recombinant adenovirus-respiratory syncytial virus vaccines with adenovirus types 4, 5, and 7 vectors in dogs and a chimpanzee.

Recombinant adenovirus type 4, 5, and 7 expressing the fusion glycoprotein (F) gene, the attachment glycoprotein (G) gene, or both F and G genes of respiratory syncytial virus (RSV) was constructed. Intratracheal immunization of dogs with Ad7F induced moderate titers of RSV-neutralizing antibodies. After booster immunization with Ad4F, the dogs developed high titers of RSV-specific antibody. Subsequently, three two-dose vaccination regimens, Ad4F/Ad5F, Ad7G/Ad4G, and Ad7FG/Ad4FG, were compared with Ad7F/Ad4F for immunogenicity and protective efficacy. The results indicated that Ad4F/Ad5F was equal or greater in immunogenicity to Ad7F/Ad4F, but Ad7G/Ad4G and Ad7FG/Ad4FG were less effective than Ad7F/Ad4F in inducing RSV-neutralizing antibody. All vaccination regimens completely protected the lungs of dogs from RSV infection. A chimpanzee was sequentially immunized orally with Ad7F, Ad4F, and Ad5F. A low-level antibody response to RSV was induced after the primary immunization, but no significant increases were observed after booster immunizations.

Adenoviruses, Human↗
PubMed1992

Reduced infectivity of cold-adapted influenza A H1N1 viruses in the elderly: correlation with serum and local antibodies.

OBJECTIVE: To compare young and elderly adults in terms of their immune responses and rates of infection following intranasal vaccination with a live attenuated influenza virus. DESIGN: Time series, comparing outcomes in young and elderly convenience sample. METHOD: Retrospective laboratory analysis of serum and nasal wash specimens collected during prior studies in which young or elderly volunteers had been inoculated with cold-adapted influenza A/Kawasaki/86 (H1N1) reassortant virus. SETTING: Johns Hopkins Center for Immunization Research. PARTICIPANTS: Healthy young and elderly adults with pre-vaccination serum hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8. OUTCOME MEASUREMENTS: Antibody responses in serum and nasal washes. MAIN RESULTS: The proportion of vaccinees who developed any serum or local antibody response was higher in young compared with elderly subjects (20/20 vs 5/14, P less than 0.0005). Resistance to infection with cold-adapted virus correlated with pre-vaccination levels of serum immunoglobulin G (IgG), serum IgA, and nasal wash IgA antibody to whole virus antigen. Age was highly correlated with a lack of response to vaccine by simple regression, but not when data were adjusted for pre-existing antibody levels. CONCLUSIONS: Cold-adapted reassortant influenza A H1N1 viruses achieve lower rates of infection in elderly than young adults, primarily due to age-related differences in preexisting levels of immunity which may not be reflected by HAI titer.

Administration, Intranasal↗
PubMed1992

Use of single-gene reassortant viruses to study the role of avian influenza A virus genes in attenuation of wild-type human influenza A virus for squirrel monkeys and adult human volunteers.

The transfer of six internal RNA segments from the avian influenza A/Mallard/New York/6750/78 (H2N2) virus reproducibly attenuates human influenza A viruses for squirrel monkeys and adult humans. To identify the avian influenza A virus genes that specify the attenuation and host range restriction of avian-human (ah) influenza A reassortant viruses (referred to as ah reassortants), we isolated six single-gene reassortant viruses (SGRs), each having a single internal RNA segment of the influenza A/Mallard/New York/6750/78 virus and seven RNA segments from the human influenza A/Los Angeles/2/87 (H3N2) wild-type virus. To assess the level of attenuation, we compared each SGR with the A/Los Angeles/2/87 wild-type virus and a 6-2 gene ah reassortant (having six internal RNA segments from the avian influenza A virus parent and two genes encoding the hemagglutinin and neuraminidase glycoproteins from the wild-type human influenza A virus) for the ability to replicate in seronegative squirrel monkeys and adult human volunteers. In monkeys and humans, replication of the 6-2 gene ah reassortant was highly restricted. In humans, the NS, M, PB2, and PB1 SGRs each replicated significantly less efficiently (P less than 0.05) than the wild-type human influenza A virus parent, suggesting that each of these genes contributes to the attenuation phenotype. In monkeys, only the NP, PB2, and possibly the M genes contributed to the attenuation phenotype. These discordant observations, particularly with regard to the NP SGR, indicate that not all genetic determinants of attenuation of influenza A viruses for humans can be identified during studies of SGRs conducted with monkeys. The PB2 and M SGRs that were attenuated in humans each exhibited a new phenotype that was not observed for either parental virus. Thus, it was not possible to determine whether avian influenza virus PB2 or M gene itself or a specific constellation of avian and human influenza A virus specified restriction of virus replication in humans.

Adult↗
PubMed1992

Comparison of different approaches to measuring influenza A virus-specific hemagglutination inhibition antibodies in the presence of serum inhibitors.

The A/Los Angeles/2/87 (H3N2) (A/LA/2/87) virus is sensitive to inhibitors of hemagglutination present in certain human sera. It was found that the effect of these inhibitors could be removed by treating sera with high-concentration receptor-destroying enzyme or trypsin-periodate or by using inhibitor-resistant viruses in the hemagglutination inhibition (HAI) test. Inhibitor-resistant viruses were not effective for detecting rises in antibody titers in the sera of volunteers infected with the A/LA/2/87 wild-type virus, while rises in antibody titer were readily detected in sera treated with trypsin-periodate and tested against A/LA/2/87 wild-type virus in an HAI test. It is therefore suggested that chemical or enzymatic methods be used to inactivate serum inhibitors and that standard virus be used in the HAI test for the currently circulating H3N2 viruses.

Antibodies, Viral↗
PubMed1992

Pulmonary histopathology induced by respiratory syncytial virus (RSV) challenge of formalin-inactivated RSV-immunized BALB/c mice is abrogated by depletion of CD4+ T cells.

In previous studies, it was observed that children immunized with a formalin-inactivated respiratory syncytial virus vaccine (FI-RSV) developed severe pulmonary disease with greater frequency during subsequent natural RSV infection than did controls. During earlier efforts to develop an animal model of this phenomenon, enhanced pulmonary histopathology was observed after intranasal RSV challenge of FI-RSV-immunized cotton rats. Progress in understanding the immunologic basis for these observations has been hampered by the lack of reagents useful in manipulating the immune response of the cotton rat. This problem prompted us to reinvestigate the characteristics of immunity to RSV in the mouse. In the present studies, extensive pulmonary histopathology was observed in FI-RSV-immunized or RSV-infected BALB/c mice upon RSV challenge, and studies to determine the relative contributions of CD4+ or CD8+ T cells to this process were undertaken. Mice previously immunized with FI-RSV or infected with RSV were depleted of CD4+, CD8+, or both T-cell subsets immediately prior to RSV challenge, and the magnitude of inflammatory cell infiltration around bronchioles and pulmonary blood vessels and into alveolar spaces was quantified. The magnitude of infiltration at each anatomic site in previously FI-RSV-immunized or RSV-infected, nondepleted animals was similar, indicating that this is not a relevant model for enhanced disease. However, the effect of T-cell subset depletion on pulmonary histopathology following RSV challenge was very different between the two groups. Depletion of CD4+ T cells completely abrogated pulmonary histopathology in FI-RSV-immunized mice, whereas it had a much smaller effect on mice previously infected with RSV. FI-RSV-immunized or RSV-infected animals depleted of CD8+ T cells had only a modest reduction of pulmonary histopathology. In addition, RSV infection induced high levels of major histocompatibility complex class I-restricted cytotoxic T-cell activity, whereas FI-RSV immunization induced a low level. These data indicate that immunization with FI-RSV induces a cellular immune response different from that induced by RSV infection, which likely played a role in enhanced disease observed in infants and children.

Animals↗
PubMed1992

Resistance to respiratory syncytial virus (RSV) challenge induced by infection with a vaccinia virus recombinant expressing the RSV M2 protein (Vac-M2) is mediated by CD8+ T cells, while that induced by Vac-F or Vac-G recombinants is mediated by antibodies.

It was previously demonstrated that the vaccinia virus recombinants expressing the respiratory syncytial virus (RSV) F, G, or M2 (also designated as 22K) protein (Vac-F, Vac-G, or Vac-M2, respectively) induced almost complete resistance to RSV challenge in BALB/c mice. In the present study, we sought to identify the humoral and/or cellular mediators of this resistance. Mice were immunized by infection with a single recombinant vaccinia virus and were subsequently given a monoclonal antibody directed against CD4+ or CD8+ T cells or gamma interferon (IFN-gamma) to cause depletion of effector T cells or IFN-gamma, respectively, at the time of RSV challenge (10 days after immunization). Mice immunized with Vac-F or Vac-G were completely or almost completely resistant to RSV challenge after depletion of both CD4+ and CD8+ T cells prior to challenge, indicating that these cells were not required at the time of virus challenge for expression of resistance to RSV infection induced by the recombinants. In contrast, the high level of protection of mice immunized with Vac-M2 was completely abrogated by depletion of CD8+ T cells, whereas depletion of CD4+ T cells or IFN-gamma resulted in intermediate levels of resistance. These results demonstrate that antibodies are sufficient to mediate the resistance to RSV induced by the F and G proteins, whereas the resistance induced by the M2 protein is mediated primarily by CD8+ T cells, with CD4+ T cells and IFN-gamma also contributing to resistance.

Animals↗
PubMed1991

An influenza A virus containing influenza B virus 5' and 3' noncoding regions on the neuraminidase gene is attenuated in mice.

Influenza A and B viruses have not been shown to form reassortants. It had been assumed that the lack of genotypic mixing between influenza virus types reflected differences in polymerase and packaging specificity. In this study, we show that an influenza A virus polymerase transcribes and replicates a chloramphenicol acetyltransferase (CAT) gene flanked by the nontranslated sequences of an influenza B virus gene. Although the transcription level of this CAT gene was several times lower than that of a CAT gene flanked by the homologous nontranslated sequences of an influenza A virus, we proceeded to construct a chimeric type A/B influenza virus. Using recombinant DNA techniques, a chimeric neuraminidase gene was introduced into the genome of influenza A/WSN/33 virus. The hybrid influenza A/B virus gene contained the coding region of the A/WSN neuraminidase and the 3' and 5' nontranslated sequences of the nonstructural gene of influenza B/Lee virus. The resulting chimeric virus formed plaques in Madin-Darby bovine kidney cells but replicated more slowly and achieved lower titers than wild-type influenza A/WSN/33 virus. The chimeric virus was attenuated for mice as indicated by a 400-fold increase in its LD50. Interestingly, the virus was greatly restricted in replication in the upper respiratory tract and partially restricted in the lungs. Animals infected with the transfectant virus were highly resistant to influenza virus challenge. It appears that this chimeric virus has many of the properties desirable for a live attenuated virus vaccine.

Animals↗
PubMed1991

Characterization of the attenuating M and NP gene segments of the avian influenza A/Mallard/78 virus during in vitro production of avian-human reassortant vaccine viruses and after replication in humans and primates.

A unique requirement for live attenuated reassortant influenza vaccines is the need to generate new reassortant vaccine viruses with the appearance of each new antigenic variant. Thus, the attenuation phenotype conferred by the attenuated donor influenza virus must remain genetically stable during the generation of each new reassortant vaccine virus. In this study we used nucleotide sequence analysis to evaluate the genetic stability of the attenuating M and NP genes of the avian influenza A/Mallard/NY/6750/78 attenuated donor virus during the in vitro generation and subsequent in vivo replication of avian-human (AH) influenza A reassortant vaccine viruses in monkeys and humans. Nucleotide sequence changes in the M and NP genes occurred at a rate of approximately 0.61 substitutions/1000 nt/reassortant during in vitro generation of four AH reassortant viruses. Only two nucleotide sequence changes occurred in the M and NP gene segments of four isolates of H1N1 or H3N2 AH vaccine viruses following 6-8 days of replication in seronegative children, and neither change affected amino acids previously identified as playing a potential role in attenuation. In addition, there were no changes in the nucleotide sequence of the M and NP genes of single gene AH reassortant viruses following five serial passages in squirrel monkeys. Finally, there was no change in the level or duration of replication of the single gene reassortant viruses in the upper or lower respiratory tract of monkeys following serial passage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Effect of passive antibody on the immune response of cotton rats to purified F and G glycoproteins of respiratory syncytial virus (RSV).

The effect of passively transferred RSV immune serum on the antibody response to a single dose of purified RSV fusion (F) and large (G) glycoproteins was studied in cotton rats. Passively transferred antibody that achieved serum antibody levels similar to those seen in newborn human infants resulted in a seven- to eightfold suppression of the neutralizing antibody response of cotton rats to low doses of purified F and G glycoproteins (0.2-1.7 micrograms) and a twofold suppression to higher doses of these antigens (5-15 micrograms). This suppression of the antibody response was accompanied by a reduction in the protective efficacy of the F and G purified glycoprotein vaccine. These results suggest that parenteral immunization with RSV antigens could be less immunogenic in seropositive human infants, but that this suppressive effect might be partially overcome with increased antigen dose.

Animals↗
PubMed1991

Protection of cotton rats by immunization with the human parainfluenza virus type 3 fusion (F) glycoprotein expressed on the surface of insect cells infected with a recombinant baculovirus.

The antigenicity, immunogenicity and efficacy of the human PIV3 fusion (F) glycoprotein expressed in insect cells by a baculovirus vector were studied. The results indicate that the PIV3 F glycoprotein expressed by a recombinant baculovirus is antigenically authentic as determined using a panel of PIV3 F specific monoclonal antibodies. Only a low level of antibody was stimulated by immunization of animals with infected cells, but the antibody appeared to be of high quality. Immunized animals were also moderately protected against PIV3 challenge. These results indicate that the baculovirus expression system is a reasonable source of authentic PIV3 F protein for use in a subunit vaccine.

Animals↗
PubMed1991

Safety and immunogenicity of live attenuated cold-adapted influenza B/Ann Arbor/1/86 reassortant virus vaccine in infants and children.

A cold-adapted (ca) influenza B reassortant vaccine consisting of two genes encoding the hemagglutinin and neuraminidase from wild-type influenza B/Ann Arbor/1/86 virus and the six internal RNA segments from influenza B/Ann Arbor/1/66 ca virus was evaluated in 18 seropositive and 57 seronegative infants and children. The ca reassortant was infectious in seronegative vaccinees, with an estimated 50% human infectious dose of 10(2.5) TCID50. Nasal wash specimens from vaccinees retained the temperature-sensitive phenotype, indicating that the virus was phenotypically stable after replication in fully susceptible children. The vaccine was highly immunogenic in the seronegative vaccinees; 54% of the seropositive vaccinees also developed an increase in serum antibody. The ca vaccine was well tolerated, with only a mild increase in upper respiratory tract symptoms seen in the seronegative vaccinees. These studies indicate that the B/Ann Arbor/1/86 ca reassortant is safe, immunogenic, and phenotypically stable in infants and children.

Antibodies, Viral↗
PubMed1991

The A/Mallard/6750/78 avian-human, but not the A/Ann Arbor/6/60 cold-adapted, influenza A/Kawasaki/86 (H1N1) reassortant virus vaccine retains partial virulence for infants and children.

Characteristics of avian-human (ah) and cold-adapted (ca) influenza A/Kawasaki/9/86 (H1N1) reassortant vaccine viruses were compared in 37 seronegative adults and 122 seronegative infants and children. The 50% human infectious dose (HID50) in infants and children was 10(2.9) and 10(2.6) TCID50 for the ah and ca vaccine, respectively. The ah influenza A/Kawasaki/9/86 reassortant was reactogenic: 24% of infants and children infected with greater than or equal to 100 HID50 had fever greater than or equal to 39.4 degrees C. Since H3N2 ah vaccines were previously shown to be adequately attenuated, it is reasonable to suggest that the genes that code for hemagglutinin and neuraminidase of the H1N1 virus apparently influence the reactogenicity of reassortant viruses derived from the avian influenza A/Mallard/New York/6750/78 donor virus. Because this avian virus does not reproducibly confer a satisfactory level of attenuation to each subtype of influenza A virus, it is not a suitable donor virus for attenuation of wild-type influenza viruses. In contrast, the ca A/Ann Arbor/6/60 donor virus reliably confers attenuation characteristics to a variety of H1N1 and H3N2 influenza A viruses.

Adult↗
PubMed1991

Group-specific serum antibody responses in children with primary and recurrent respiratory syncytial virus infections.

Antigenic group-specific serum antibody responses to first and second respiratory syncytial virus (RSV) infections were studied in children who had been followed longitudinally from early infancy in a research day-care center. Plaque-reduction neutralizing (PRN) antibody assays and ELISAs for the fusion (F) and attachment (G) glycoproteins were done using antigens of prototype RSV strains from groups A and B. Responses to antigens of viruses homologous and heterologous to the antigenic group of the infecting viral strain were compared. Primary group A infection elicited antibodies cross-reactive with group B virus in the PRNB and the ELISAS for GB and FB. In contrast, primary group B infection induced significant increases in mean concentrations of antibody cross-reactive with group A virus only in the FA ELISA. Second RSV infections caused by group B viruses in children with histories of primary group A infection induced heterologous rises in the PRNA and GA assays, suggesting that prior group A infection had primed for a more extensive cross-reacting antibody response at the time of second RSV infections with group B viruses.

Antibodies, Viral↗
PubMed1991

In elderly persons live attenuated influenza A virus vaccines do not offer an advantage over inactivated virus vaccine in inducing serum or secretory antibodies or local immunologic memory.

In a double-blind, randomized trial, 102 healthy elderly subjects were inoculated with one of four preparations: (i) intranasal bivalent live attenuated influenza vaccine containing cold-adapted A/Kawasaki/86 (H1N1) and cold-adapted A/Bethesda/85 (H3N2) viruses; (ii) parenteral trivalent inactivated subvirion vaccine containing A/Taiwan/86 (H1N1), A/Leningrad/86 (H3N2), and B/Ann Arbor/86 antigens; (iii) both vaccines; or (iv) placebo. To determine whether local or systemic immunization augmented mucosal immunologic memory, all volunteers were challenged intranasally 12 weeks later with the inactivated virus vaccine. We used a hemagglutination inhibition assay to measure antibodies in sera and a kinetic enzyme-linked immunosorbent assay to measure immunoglobulin G (IgG) and IgA antibodies in sera and nasal washes, respectively. In comparison with the live virus vaccine, the inactivated virus vaccine elicited higher and more frequent rises of serum antibodies, while nasal wash antibody responses were similar. The vaccine combination induced serum and local antibodies slightly more often than the inactivated vaccine alone did. Coadministration of live influenza A virus vaccine did not alter the serum antibody response to the influenza B virus component of the inactivated vaccine. The anamnestic nasal antibody response elicited by intranasal inactivated virus challenge did not differ in the live, inactivated, or combined vaccine groups from that observed in the placebo group not previously immunized. These results suggest that in elderly persons cold-adapted influenza A virus vaccines offer little advantage over inactivated virus vaccines in terms of inducing serum or secretory antibody or local immunological memory. Studies are needed to determine whether both vaccines in combination are more efficacious than inactivated vaccine alone in people in this age group.

Administration, Intranasal↗
PubMed1991

Evaluation of bovine, cold-adapted human, and wild-type human parainfluenza type 3 viruses in adult volunteers and in chimpanzees.

In an attempt to evaluate the level of attenuation of live parainfluenza type 3 virus (PIV3) vaccine candidates, we compared the responses of partially immune adult volunteers inoculated intranasally with 10(6) to 10(7) 50% tissue culture infective dose (TCID50) of bovine PIV3 (n = 18) or cold-adapted (ca) PIV3 (n = 37) with those of 28 adults administered 10(6) to 10(7) TCID50 of wild-type PIV3. The candidate vaccine viruses and the wild-type virus were avirulent and poorly infectious for these adults even though all of them had a low level of nasal antibodies to PIV3. To determine whether the ca PIV3 was attenuated, we then administered 10(4) TCID50 of ca PIV3 (cold-passage 12) or wild-type PIV3 intranasally and intratracheally to two fully susceptible chimpanzees, respectively, and challenged the four primates with wild-type virus 1 month later. Compared with wild-type virus, which caused upper respiratory tract illness, the ca PIV3 was highly attenuated and manifested a 500-fold reduction in virus replication in both the upper and lower respiratory tracts of the two immunized animals. Despite restriction of virus replication, infection with ca PIV3 conferred a high level of protective immunity against challenge with wild-type virus. The ca PIV3 which had been passaged 12 times at 20 degrees C did not retain its ts phenotype. These findings indicate that ca PIV3 may be a promising vaccine candidate for human beings if a passage level can be identified that is genetically stable, satisfactorily attenuated, and immunogenic.

Adaptation, Physiological↗
PubMed1991

Effectiveness of enteric immunization in the development of secretory immunoglobulin A response and the outcome of infection with respiratory syncytial virus.

Cotton rats were immunized via intranasal, intradermal, or enteric routes with respiratory syncytial virus (RSV) or a live recombinant vaccinia virus expressing the RSV F glycoprotein (vaccinia F). The animals were tested for the appearance of RSV-specific antibody responses in the serum, bronchoalveolar lavage, and nasal wash after immunization and for virus replication 4 days after intranasal challenge with RSV. RSV antibody response in the serum and respiratory tract was demonstrated in all immunization groups and was significantly increased after intranasal challenge with RSV. Immunoglobulin A (IgA) antibody response in bronchoalveolar lavage fluid after intranasal or enteric immunization was two- to threefold higher than that after intradermal immunization. Nasal-wash IgA antibody response was not significantly different among three immunization groups, although mean antibody titer was the highest in intranasal immunization group. Complete resistance to replication of RSV challenge was observed in the lungs of cotton rats immunized by the intranasal or enteric routes, whereas a low level of replication was detected in the lungs of rats immunized intradermally. Enteric or intradermal immunization conferred partial protection to the upper respiratory tract, but complete protection of the upper respiratory tract was observed in the intranasal immunization group. These observations suggest that while enteric immunization is quite effective in inducing antibody responses in the respiratory tract, the magnitude of antiviral immunity induced in the respiratory tract after intranasal immunization may be superior to that observed after enteric immunization.

Animals↗