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Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires antibodies against both hemagglutinin and neuraminidase in mice.
J Infect Dis. 2009 Jun 01; 199(11):1629-37.JI

Abstract

BACKGROUND

Hemagglutination-inhibition (HI) antibody titers correlate with protective immunity to seasonal influenza viruses. However, inactivated H5N1 influenza vaccines from Vietnam 2004 strains afford protection without producing high or even detectable HI antibodies.

METHODS

BALB/c mice were immunized twice (at a 3-week interval) with inactivated whole-virus influenza vaccine produced using reverse genetics, with the internal genes of A/PR/8/34 (a high-yield strain) and the hemagglutinin (HA) and neuraminidase (NA) genes of A/Vietnam/1194/04 (H5N1) virus (NIBRG-14) adjuvanted with alum (5 microg of HA). Either HA- or NA-binding antibodies were absorbed from the immune serum. The protective efficacy of these antibodies was determined by injecting the absorbed serum into severe combined immunodeficiency mice, which were then challenged with highly pathogenic H5N1 virus (A/Vietnam/Jp1203/2004; Japanese isolate of A/Vietnam/1203/2004).

RESULTS

The NIBRG-14 vaccine elicited levels of anti-HA antibodies similar to levels elicited by the H1N1 vaccines, as well as levels of anti-NA antibodies higher than those elicited by the H1N1 vaccines. The absorption of either anti-HA or anti-NA antibody from immune serum samples obtained from NIBRG-14-vaccinated mice significantly reduced the protective efficacy of the serum.

CONCLUSIONS

For NIBRG-14 vaccines to confer protection to vaccinated hosts, both anti-HA and anti-NA antibodies are required. This finding implies that the measurement of both antibody levels may be required for accurate evaluation of vaccine efficacy.

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Authors+Show Affiliations

Takahashi Y
Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan. ytakahas@nih.go.jp
Hasegawa H
No affiliation info available
Hara Y
No affiliation info available
Ato M
No affiliation info available
Ninomiya A
No affiliation info available
Takagi H
No affiliation info available
Odagiri T
No affiliation info available
Sata T
No affiliation info available
Tashiro M
No affiliation info available
Kobayashi K
No affiliation info available

MeSH

AnimalsAntibodies, ViralFlow CytometryHemagglutination, ViralInfluenza A Virus, H5N1 SubtypeMiceMice, Inbred BALB CNeuraminidaseOrthomyxoviridae InfectionsVaccines, Inactivated

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19385735

Citation

Takahashi, Yoshimasa, et al. "Protective Immunity Afforded By Inactivated H5N1 (NIBRG-14) Vaccine Requires Antibodies Against Both Hemagglutinin and Neuraminidase in Mice." The Journal of Infectious Diseases, vol. 199, no. 11, 2009, pp. 1629-37.
Takahashi Y, Hasegawa H, Hara Y, et al. Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires antibodies against both hemagglutinin and neuraminidase in mice. J Infect Dis. 2009;199(11):1629-37.
Takahashi, Y., Hasegawa, H., Hara, Y., Ato, M., Ninomiya, A., Takagi, H., Odagiri, T., Sata, T., Tashiro, M., & Kobayashi, K. (2009). Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires antibodies against both hemagglutinin and neuraminidase in mice. The Journal of Infectious Diseases, 199(11), 1629-37. https://doi.org/10.1086/598954
Takahashi Y, et al. Protective Immunity Afforded By Inactivated H5N1 (NIBRG-14) Vaccine Requires Antibodies Against Both Hemagglutinin and Neuraminidase in Mice. J Infect Dis. 2009 Jun 1;199(11):1629-37. PubMed PMID: 19385735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective immunity afforded by inactivated H5N1 (NIBRG-14) vaccine requires antibodies against both hemagglutinin and neuraminidase in mice. AU - Takahashi,Yoshimasa, AU - Hasegawa,Hideki, AU - Hara,Yukari, AU - Ato,Manabu, AU - Ninomiya,Ai, AU - Takagi,Hirotaka, AU - Odagiri,Takato, AU - Sata,Tetsutaro, AU - Tashiro,Masato, AU - Kobayashi,Kazuo, PY - 2009/4/24/entrez PY - 2009/4/24/pubmed PY - 2009/7/29/medline SP - 1629 EP - 37 JF - The Journal of infectious diseases JO - J Infect Dis VL - 199 IS - 11 N2 - BACKGROUND: Hemagglutination-inhibition (HI) antibody titers correlate with protective immunity to seasonal influenza viruses. However, inactivated H5N1 influenza vaccines from Vietnam 2004 strains afford protection without producing high or even detectable HI antibodies. METHODS: BALB/c mice were immunized twice (at a 3-week interval) with inactivated whole-virus influenza vaccine produced using reverse genetics, with the internal genes of A/PR/8/34 (a high-yield strain) and the hemagglutinin (HA) and neuraminidase (NA) genes of A/Vietnam/1194/04 (H5N1) virus (NIBRG-14) adjuvanted with alum (5 microg of HA). Either HA- or NA-binding antibodies were absorbed from the immune serum. The protective efficacy of these antibodies was determined by injecting the absorbed serum into severe combined immunodeficiency mice, which were then challenged with highly pathogenic H5N1 virus (A/Vietnam/Jp1203/2004; Japanese isolate of A/Vietnam/1203/2004). RESULTS: The NIBRG-14 vaccine elicited levels of anti-HA antibodies similar to levels elicited by the H1N1 vaccines, as well as levels of anti-NA antibodies higher than those elicited by the H1N1 vaccines. The absorption of either anti-HA or anti-NA antibody from immune serum samples obtained from NIBRG-14-vaccinated mice significantly reduced the protective efficacy of the serum. CONCLUSIONS: For NIBRG-14 vaccines to confer protection to vaccinated hosts, both anti-HA and anti-NA antibodies are required. This finding implies that the measurement of both antibody levels may be required for accurate evaluation of vaccine efficacy. SN - 0022-1899 UR - https://www.unboundmedicine.com/medline/citation/19385735/Protective_immunity_afforded_by_inactivated_H5N1__NIBRG_14__vaccine_requires_antibodies_against_both_hemagglutinin_and_neuraminidase_in_mice_ L2 - https://academic.oup.com/jid/article-lookup/doi/10.1086/598954 DB - PRIME DP - Unbound Medicine ER -