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Respiratory Viruses Vaccine Trials at the CIR


Respiratory Syncytial Virus (RSV)

Clinical trials of RSV vaccines at the CIR have focused primarily on live attenuated vaccines developed at the Laboratory of Infectious Diseases, NIAID, NIH, with initial evaluation of biologically derived temperature sensitive mutants, and more recent evaluation of recombinant vaccines containing known attenuating point mutations and/or deletion of nonessential genes. Live attenuated candidate vaccines for RSV have been evaluated at the CIR in adults, children, and infants include:

  • Temperature sensitive viruses derived by serial passage at low temperature, including:

RSV A2 strains cpts 248/955, cpts 530/1009, cpts 248/404

  • Recombinant viruses containing known attenuating point mutations and/or deletion of nonessential genes, including:

rA2cp248/404/deltaSH

rA2cp248/404/1030/deltaSH

rA2cp248/404/deltaNS2

Here is a link to a list of selected publications by CIR faculty about RSV.


Pandemic / Avian  Influenza

Live attenuated, cold-adapted H1N1 and H3N2 influenza A/AA/6/60 ca reassortant viruses are the influenza A components of the trivalent live attenuated vaccine, FluMist, which is currently licensed for annual use for prevention of infection with interpandemic influenza. H1N1 and H3N2 influenza A/AA/6/60 ca contain internal genes from the A/AA/6/60 master donor virus (MDV) and HA and NA genes from current H1N1 and H3N2 viruses. Using the A/AA/6/60/ca MDV, the Laboratory of Infectious Diseases, NIAID, NIH and MedImmune have developed several vaccine candidates for avian influenza strains of interest.

The CIR has and will be conducting inpatient studies in healthy adults to investigate the safety, infectivity, and immunogenicity of these vaccines candidates which target H5N1, H9N2,  H7N3, H2N2, and H6N1 viruses.

Trials completed to date include:

  • Live attenuated, cold-adapted H9N2 (6-2) AA ca reassortant (A/chicken/Hong Kong/G9/97 x A/Ann Arbor/6/60 ca)
  • Live attenuated cold-adapted H5N1 (6-2) AA ca recombinant (A/VietNam/1203/2004 x A/Ann Arbor/6/60 ca)
  • Live attenuated cold-adapted H5N1 (6-2) AA ca recombinant (A/Hong Kong/213/2003 x A/Ann Arbor/6/60 ca)
  • Live attenuated cold-adapted H7N3 (6-2) AA ca recombinant (A/chicken/British Columbia/CN-6/2004 x A/Ann Arbor/6/60 ca)
  • Live attenuated cold-adapted H2N2 (A/Ann Arbor/6/60 ca recombinant)
  • Live attenuated cold-adapted H6N1(6-2) AA ca recombinant (A/teal/Hong Kong/1997 x A/Ann Arbor/6/60 ca)

Here is a link to a list of selected publications by CIR faculty about pandemic influenza vaccines.


Human Parainfluenza Viruses (HPIV)

Several live attenuated candidate vaccines for human parainfluenza virus type 3 (HPIV3) have been evaluated at the CIR in adults, children, and infants.  These include:

  • Temperature sensitive viruses derived by serial passage at low temperature (cp-18 HPIV3 and cp-45 HPIV3)
  • Bovine PIV-3 (BPIV3)
  • Recombinant chimeric HPIV3/BPIV3 viruses containing the surface hemagglutinin-neuraminidase (HN) and fusion (F) glycoproteins from HPIV3 and one or more attenuating internal genes from BPIV3 (rB/HPIV3 (F&HN ) hu and rHPIV3-Nb).

cp-45 and its recombinant version, rcp45, appear to be highly attenuated and induce antibody responses in infants as young as one month of age.  Phase I evaluation of the recombinant chimeric HPIV3/BPIV3 vaccine viruses is in progress.

In addition to vaccines against HPIV3, we are also evaluating live attenuated recombinant vaccines against human parainfluenza viruses types 1 and 2, which are the principle etiologic agents of croup in young children.

Here is a link to a list of selected publications by CIR faculty about HPIV.

   Topics

RSV

Pandemic Influenza

HPIV

Respiratory Viruses Vaccine Trials