Squalene-containing licensed adjuvants enhance strain-specific antibody responses against the influenza hemagglutinin and induce subtype-specific antibodies against the neuraminidase

Schmidt, Rebecca; Holznagel, Edgar; Neumann, Britta; Alex, Nina; Sawatsky, Bevan; Enkirch, Theresa; Pfeffermann, Kristin; Kruip, Carina; Messling, Véronika von; Wagner, Ralf

doi:10.1016/j.vaccine.2016.08.082

Cited by 5 publications

(11 citation statements)

References 38 publications

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“…Using the data from Schmidt et al . 17 , we fit our model parameters to virus-neutralizing antibody titers, and qualitatively compare our results to the experimentally observed protein-specific titers. Our simulation results show that this simple model is able to recapitulate the essential features of antibody production elicited by adjuvanted vaccine formulations, and may serve as a stepping stone for more complex analyses.…”

Section: Introductionmentioning

confidence: 89%

“…For the proposed mathematical modeling analysis, the experimental data previously published by Schmidt et al . 17 is employed. Briefly, adult male and female ferrets, immunologically naive to circulating influenza strains, were immunized intramuscularly with adjuvanted and non-adjuvanted formulations of the inactivated pandemic H1N1pdm09 vaccine, followed by a boost 3 weeks later.…”

Section: Methodsmentioning

confidence: 99%

“…Specifically, we fit the output of the model defined by Eqs (1) and (2), y (model) , to the data from Schmidt et al . 17 corresponding to the virus-neutralizing antibody titers as a function of time following vaccination and immunization boost. This is compared to the total area under the curve of the distribution given by Ab ( x , t ); that is, .…”

Section: Methodsmentioning

confidence: 99%

“…This may be addressed by antigen-sparing strategies in combination with adjuvants, which trigger a strong immune response at lower antigen doses than otherwise necessary 16 . Interestingly, the addition of squalene-containing adjuvants has also been observed positively influence the breadth of the antibody response by enhancing not only the overall titers but also the production of antibodies that target the NA protein 17 . Since NA is more conserved, antibodies directed towards this protein may confer partial immunity against other influenza strains carrying the same NA subtype 18 .…”

Section: Introductionmentioning

confidence: 99%

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Adjuvanted influenza vaccine dynamics

Parra‐Rojas

Messling

Hernandez‐Vargas

2019

Sci Rep

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Adjuvanted influenza vaccines constitute a key element towards inducing neutralizing antibody responses in populations with reduced responsiveness, such as infants and elderly subjects, as well as in devising antigen-sparing strategies. In particular, squalene-containing adjuvants have been observed to induce enhanced antibody responses, as well as having an influence on cross-reactive immunity. To explore the effects of adjuvanted vaccine formulations on antibody response and their relation to protein-specific immunity, we propose different mathematical models of antibody production dynamics in response to influenza vaccination. Data from ferrets immunized with commercial H1N1pdm09 vaccine antigen alone or formulated with different adjuvants was instrumental to adjust model parameters. While the affinity maturation process complexity is abridged, the proposed model is able to recapitulate the essential features of the observed dynamics. Our numerical results suggest that there exists a qualitative shift in protein-specific antibody response, with enhanced production of antibodies targeting the NA protein in adjuvanted versus non-adjuvanted formulations, in conjunction with a protein-independent boost that is over one order of magnitude larger for squalene-containing adjuvants. Furthermore, simulations predict that vaccines formulated with squalene-containing adjuvants are able to induce sustained antibody titers in a robust way, with little impact of the time interval between immunizations.

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Section: Introductionmentioning

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Adjuvanted influenza vaccine dynamics

Parra‐Rojas

Messling

Hernandez‐Vargas

2019

Sci Rep

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“…The inclusion of adjuvants also reduces the volume of antigen needed per vaccine dose through the process of “antigen sparing,” maximizing rates of vaccine production (Tang et al. 2015; Schmidt et al 2016). Although the primary global demand for shark liver oil in recent years appears to be for use in cosmetics and lotions (Vannuccini 1999; Lozano-Grande et al, 2018), the role of shark-derived squalene in vaccine production may represent a potential threat to some vulnerable shark populations, given widespread efforts to rapidly develop and disseminate vaccines in response to the COVID-19 pandemic and the patchwork management approach to global shark fishing limits (Ahn et al, 2020; Hodgson, 2020; Davidson et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Shark conservation risks associated with the use of shark liver oil in SARS-CoV-2 vaccine development

Macdonald

Soll

2020

Preprint

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The COVID-19 pandemic may create new demand for wildlife-generated products for human health, including a shark-derived ingredient used in some vaccines. Adjuvants are a vaccine component that increases efficacy, and some adjuvants contain squalene, a natural compound derived from shark liver oil which is found most abundantly in deep-sea sharks. In recent decades, there has been growing conservation concern associated with the sustainability of many shark fisheries. The need for a potentially massive number of adjuvant-containing SARS-CoV-2 vaccines may increase global demand for shark-derived squalene, with possible consequences for shark conservation, especially of vulnerable and understudied deep-sea species. A shift to non-animal-derived sources of squalene, which are similar in cost and identical in effectiveness, or an emphasis on increasing traceability and sustainability of shark-derived squalene from existing well-managed fisheries, could better support conservation and public health goals.

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