ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

Luca Schifanella; Susan W Barnett; Massimiliano Bissa; Veronica Galli; Melvin N Doster; Monica Vaccari; Georgia D Tomaras; Xiaoying Shen; Sanjay Phogat; Ranajit Pal; David C Montefiori; Celia C LaBranche; Mangala Rao; Hung V Trinh; Robyn Washington-Parks; Namal P M Liyanage; Giacomo Gorini; Dallas R Brown; Frank Liang; Karin Loré; David J Venzon; William Magnanelli; Michelle Metrinko; Josh Kramer; Matthew Breed; Galit Alter; Ruth M Ruprecht; Genoveffa Franchini

doi:10.1371/journal.ppat.1008121

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

Luca Schifanella, Susan W Barnett, Massimiliano Bissa, Veronica Galli, Melvin N Doster, Monica Vaccari, Georgia D Tomaras, Xiaoying Shen, Sanjay Phogat, Ranajit Pal, David C Montefiori, Celia C LaBranche, Mangala Rao, Hung V Trinh, Robyn Washington-Parks, Namal P M Liyanage, Giacomo Gorini, Dallas R Brown, Frank Liang, Karin LoréDavid J Venzon, William Magnanelli, Michelle Metrinko, Josh Kramer, Matthew Breed, Galit Alter, Ruth M Ruprecht, Genoveffa Franchini

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14 Scopus citations

Abstract

The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

Original language	English (US)
Pages (from-to)	e1008121
Journal	PLoS pathogens
Volume	15
Issue number	12
DOIs	https://doi.org/10.1371/journal.ppat.1008121
State	Published - Dec 2019
Externally published	Yes

Keywords

AIDS Vaccines/chemistry
Adjuvants, Immunologic/pharmacology
Alum Compounds/pharmacology
Animals
Antibodies, Neutralizing/immunology
Antibodies, Viral/immunology
Female
HIV Infections
Macaca mulatta
SAIDS Vaccines/chemistry
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
Viral Vaccines/chemistry

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Schifanella, L., Barnett, S. W., Bissa, M., Galli, V., Doster, M. N., Vaccari, M., Tomaras, G. D., Shen, X., Phogat, S., Pal, R., Montefiori, D. C., LaBranche, C. C., Rao, M., Trinh, H. V., Washington-Parks, R., Liyanage, N. P. M., Gorini, G., Brown, D. R., Liang, F., ... Franchini, G. (2019). ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. PLoS pathogens, 15(12), e1008121. https://doi.org/10.1371/journal.ppat.1008121

Schifanella, L, Barnett, SW, Bissa, M, Galli, V, Doster, MN, Vaccari, M, Tomaras, GD, Shen, X, Phogat, S, Pal, R, Montefiori, DC, LaBranche, CC, Rao, M, Trinh, HV, Washington-Parks, R, Liyanage, NPM, Gorini, G, Brown, DR, Liang, F, Loré, K, Venzon, DJ, Magnanelli, W, Metrinko, M, Kramer, J, Breed, M, Alter, G, Ruprecht, RM & Franchini, G 2019, 'ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type', PLoS pathogens, vol. 15, no. 12, pp. e1008121. https://doi.org/10.1371/journal.ppat.1008121

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abstract = "The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.",

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AU - Schifanella, Luca

AU - Barnett, Susan W

AU - Bissa, Massimiliano

AU - Galli, Veronica

AU - Doster, Melvin N

AU - Vaccari, Monica

AU - Tomaras, Georgia D

AU - Shen, Xiaoying

AU - Phogat, Sanjay

AU - Pal, Ranajit

AU - Montefiori, David C

AU - LaBranche, Celia C

AU - Rao, Mangala

AU - Trinh, Hung V

AU - Washington-Parks, Robyn

AU - Liyanage, Namal P M

AU - Gorini, Giacomo

AU - Brown, Dallas R

AU - Liang, Frank

AU - Loré, Karin

AU - Venzon, David J

AU - Magnanelli, William

AU - Metrinko, Michelle

AU - Kramer, Josh

AU - Breed, Matthew

AU - Alter, Galit

AU - Ruprecht, Ruth M

AU - Franchini, Genoveffa

PY - 2019/12

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N2 - The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

AB - The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.

KW - AIDS Vaccines/chemistry

KW - Adjuvants, Immunologic/pharmacology

KW - Alum Compounds/pharmacology

KW - Animals

KW - Antibodies, Neutralizing/immunology

KW - Antibodies, Viral/immunology

KW - Female

KW - HIV Infections

KW - Macaca mulatta

KW - SAIDS Vaccines/chemistry

KW - Simian Acquired Immunodeficiency Syndrome

KW - Simian Immunodeficiency Virus

KW - Viral Vaccines/chemistry

U2 - 10.1371/journal.ppat.1008121

DO - 10.1371/journal.ppat.1008121

M3 - Article

C2 - 31794588

SN - 1553-7366

VL - 15

SP - e1008121

JO - PLoS pathogens

JF - PLoS pathogens

IS - 12

ER -

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type

Abstract

Keywords

PubMed: MeSH publication types

UN SDGs

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