A dose-ranging study of MF59<sup>®</sup>-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination

Reisinger, Keith S.; Holmes, Scott A.; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria

doi:10.4161/hv.29393

Cited by 23 publications

(13 citation statements)

References 33 publications

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“…A limitation of our trial design was that it did not evaluate higher doses of gp120, which may have increased the durability of the immune response. The gp120 dose administered in HVTN 100 was one-third the dose used in the RV144 trial, with the expectation that MF59 would be dose-sparing relative to the alum adjuvant [33]. There are 2 caveats in interpretation of our data.…”

Section: Discussionmentioning

confidence: 85%

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

et al. 2020

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Background HVTN 100 evaluated the safety and immunogenicity of an HIV subtype C pox-protein vaccine regimen, investigating a 12-month booster to extend vaccine-induced immune responses. Methods and findings A phase 1-2 randomized double-blind placebo-controlled trial enrolled 252 participants (210 vaccine/42 placebo; median age 23 years; 43% female) between 9 February 2015 and 26 May 2015. Vaccine recipients received ALVAC-HIV (vCP2438) alone at months 0 and 1 and

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Section: Discussionmentioning

confidence: 85%

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

et al. 2020

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“…Other than the difference in the sequences of the vaccine strains in the vector and protein immunogens for HVTN 100 and HVTN 097, the adjuvants and the protein doses differed as well: HVTN 097 used an inorganic adjuvant (aluminum hydroxide) while HVTN 100 used an organic adjuvant (MF59, an oil-in-water squalene-based emulsion with purported dose-sparing effect 38,39 ); the protein doses in HVTN 100 were 1/3 that of the protein doses in HVTN 097; and, the ALVAC dose in HVTN 097 was 2.7 times the ALVAC dose in HVTN 100. However, the stronger or similar envelope gp120 responses in HVTN 100 compared to RV144 and HVTN 097 indicate that the lower V2 binding response in HVTN 100 is likely due to vaccine strain sequence differences rather than dose and adjuvant differences that tend to affect overall binding antibody responses.…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Vaccine Sequences Impact V1V2 Antibody Responses: A Comparison of Two Poxvirus Prime gp120 Boost Vaccine Regimens

Shen

Laher

Moodie

et al. 2020

Sci Rep

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Nonhuman primate studies conducted after RV144 supported the importance of non-neutralizing antibodies to V2 for protection from experimental challenge. Vaccine-elicited V2 IgG correlated with delayed SIV 9-13 and SHIV acquisition 14 , and with viremia control after SIV infection 13. Passive transfer of 830 A, a V2-specific monoclonal antibody (mAb), resulted in improved viremia control in nonhuman primates 15. Many studies have reported antiviral functions that include antibody Fc effector functions and direct neutralization mediated by antibodies that recognize V2 7,16-22. V2-specific mAbs recognizing aa169, which were isolated from RV144 vaccine recipients, were shown to mediate tier 1 neutralization, bind to infectious virions 23 , and mediate killing of primary HIV-1 isolate infected cells 16. Aa169 is located within the linear epitope sequence bound by RV144 vaccine-elicited antibodies that correlated with decreased HIV-1 risk 4. The other known site of RV144-induced immune pressure in V2, aa181, is also part of the leucine-aspartic acid-isoleucine/valine (LDI/V) aa179-181 sequence motif reported to mediate HIV-1 envelope interaction with the gut mucosal homing integrin receptor α4β7 to facilitate cell-to-cell spread 19,20. It has been postulated that V2-specific antibodies may block or interfere with the interaction between α4β7 and the HIV-1 envelope to prevent viral transmission 19,20. In participants from the RV144 trial and the RV305 trial, in which delayed boosters were given to RV144 participants, a group of V2-specific mAbs were shown to be capable of blocking AE.92TH023 V2 peptide binding to α4β7 24. The α4β7-blocking antibodies included both those targeting the linear V2 hotspot and those targeting the conformational epitopes 25. V2-specific antibodies can mediate phagocytosis 18,26,27 and can synergize with C1-C2 specific IgG for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) 28. Furthermore, quaternary epitopes involving the V2 loop were identified as a target for broadly neutralizing antibodies 21,29. The Pox-Protein Public-Private Partnership (P5) program was established to develop a subtype C-directed vaccine based on the RV144 regimen 30. As part of this program, two phase 1/2 trials were designed in South Africa: HIV Vaccine Trials Network (HVTN) 097 31 (ClinicalTrials.gov NCT02109354) determined immune responses of an African population to the RV144 regimen, and HVTN 100 32 (ClinicalTrials.gov NCT02404311) investigated the immunogenicity of the regimen adapted to subtype C. The selection criteria for the subtype C envelope immunogens included binding and affinity by V2-specific mAbs 33,34. The HVTN 100 primary immunological data were evaluated against prespecified immunological criteria and guided the decision to proceed with the vaccine regimen into an efficacy trial, HVTN 702. Vaccine-elicited responses in HVTN 100 met all four prespecified go/no-go criteria for the continuation of the HVTN 702 trial, including the envelope-binding and V1V2-binding IgG response 32. Our stu...

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“…In human and murine studies, adjuvants and increased antigen doses have been used to generate better vaccine responses. Influenza vaccines administered with the squalene based M59 adjuvant generated higher seroprotection rates in people over 60 [24,25]. The Fluzone High-Dose vaccine formulation made by Sanofi Pasteur which contains four times the active antigen content as in the conventional vaccine received by young adults, increased seroconversion rates from 30% to 50% to H1N1 in the elderly [26].…”

Section: Introductionmentioning

confidence: 99%

CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice

Ramirez

Mathew

2016

PLoS ONE

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Several studies have shown a reduced efficacy of influenza vaccines in the elderly compared to young adults. In this study, we evaluated the immunogenicity and protective efficacy of a commercially available inactivated influenza vaccine (Fluzone®) in young adult and aged mice. C57/BL6 mice were administered a single or double immunization of Fluzone® with or without CpG and challenged intranasally with H1N1 A/California/09 virus. A double immunization of Fluzone® adjuvanted with CpG elicited the highest level of protection in young adult mice which was associated with increases in influenza specific IgG, elevated HAI titres, reduced viral titres and lung inflammation. In contrast, the vaccine schedule which provided fully protective immunity in young adult mice conferred limited protection in aged mice. Antigen presenting cells from aged mice were found to be less responsive to in vitro stimulation by Fluzone and CpG which may partially explain this result. Our data are supportive of studies that have shown limited effectiveness of influenza vaccines in the elderly and provide important information relevant to the design of more immunogenic vaccines in this age group.

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A dose-ranging study of MF59^®-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination

Cited by 23 publications

References 33 publications

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

HIV-1 Vaccine Sequences Impact V1V2 Antibody Responses: A Comparison of Two Poxvirus Prime gp120 Boost Vaccine Regimens

CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice

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A dose-ranging study of MF59®-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination

Cited by 23 publications

References 33 publications

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

Safety and immune responses after a 12-month booster in healthy HIV-uninfected adults in HVTN 100 in South Africa: A randomized double-blind placebo-controlled trial of ALVAC-HIV (vCP2438) and bivalent subtype C gp120/MF59 vaccines

HIV-1 Vaccine Sequences Impact V1V2 Antibody Responses: A Comparison of Two Poxvirus Prime gp120 Boost Vaccine Regimens

CpG Improves Influenza Vaccine Efficacy in Young Adult but Not Aged Mice

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A dose-ranging study of MF59^®-adjuvanted and non-adjuvanted A/H1N1 pandemic influenza vaccine in young to middle-aged and older adult populations to assess safety, immunogenicity, and antibody persistence one year after vaccination