Maternal immunization with adjuvanted RSV prefusion F protein effectively protects offspring from RSV challenge and alters innate and T cell immunity

Eichinger, Katherine M.; Kosanovich, Jessica L.; Lipp, Madeline A.; Perkins, Timothy N.; Petrovsky, Nikolai; Marshall, Christopher; Yondola, Mark A.; Empey, Kerry M.

doi:10.1016/j.vaccine.2020.10.065

Cited by 10 publications

(13 citation statements)

References 17 publications

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“…Our results show some similarities as well as differences with results published by Eichenger et al . performing maternal vaccination in the mice model of RSV using an RSV F protein in the prefusion conformation and adjuvanted with Advax-SM (a delta inulin-based adjuvant paired with the toll-like receptor 9 agonist, CpG oligodeoxynucleotide) 45 . In cotton rats, as in the mice model, we found an inverse correlation between IFNγ mRNA expression and neutralizing maternal antibodies early in life of pups (4 weeks).…”

Section: Discussionmentioning

confidence: 99%

Correlative outcomes of maternal immunization against RSV in cotton rats

Blanco

Cullen

Kamali

et al. 2022

Human Vaccines & Immunotherapeutics

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Maternal anti-respiratory syncytial virus (RSV) antibodies protect neonates from RSV disease throughout first weeks of life. Previous studies of maternal immunization in cotton rats showed that a single immunization during pregnancy of RSV-primed dams with virus-like particles (VLPs) assembled with pre-fusion F protein and the wild type G protein boosted their RSV serum antibody concentration and protected pups early in life against RSV challenge. We extended these findings by evaluating responses to RSV infection in litters from two consecutive pregnancies of immunized dams. Using an RSV-primed population of VLP-vaccinated and unvaccinated dams, we defined correlations between dams’ and litters’ RSV neutralizing antibodies (NA); between litters’ NA and protection; and between litter’s NA and their lung expression of selected cytokines, of a first or of a second pregnancy. Lung pathology was also evaluated. We found positive correlation between the NA titers in the dams at delivery and the NA in their first and second litters and negative correlations between the litters’ NA and protection from RSV challenge. Vaccination of dams modulated the mRNA expression for IFNγ and IL-6 and lung pathology in the first and in the second litter at different times after birth, even in the absence of detectable NA. Maternal RSV vaccination enhanced the levels of antibodies transferred to offspring and their protection from challenge. Importantly, maternal vaccination also impacted the immunological and inflammatory response of the offspring’s lungs well into maturity, and after the antiviral effect of maternally transferred NA waned or was no longer detectable.

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Section: Discussionmentioning

confidence: 99%

Correlative outcomes of maternal immunization against RSV in cotton rats

Blanco

Cullen

Kamali

et al. 2022

Human Vaccines & Immunotherapeutics

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“…The multi-country large clinical trial by MADHI et al [13] was the first to investigate maternal RSV vaccines in pregnant women; therefore, previous research evaluating RSV vaccines was not directly comparable. A trial on mice published by EICHINGER et al [15] found that offspring born to mothers vaccinated with RSV pre-F protein vaccine formulated with Advax-SM had higher levels of neutralising antibody titres compared to offspring born to mothers who received the control vaccine. When challenged with RSV exposure, those offspring also had undetectable virus in their lungs, showing evidence of the protective immunity that maternal vaccinations can offer to the offspring.…”

Section: Commentarymentioning

confidence: 99%

Efficacy of maternal vaccination during pregnancy against infant respiratory viruses

Tran

Pham

Chichirelo-Konstantynovych

et al. 2022

Breathe

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Section: Infant Rsv Immune Responsesmentioning

confidence: 99%

“…153 Hence, an optimally protective neonatal RSV vaccine without the risks of VED might be created by combining a pre-F antigen with Advax adjuvant, with such a vaccine currently under study by the authors with promising results. [154][155] Summary and conclusion RSV is the leading cause of morbidity and mortality in children worldwide. Efforts to develop an effective RSV vaccination began shortly after its discovery in the late 1950s.…”

Section: Subunit Vaccinesmentioning

confidence: 99%

Strategies for active and passive pediatric RSV immunization

Eichinger

Kosanovich

Lipp

et al. 2021

Therapeutic Advances in Vaccines and Immunotherapy

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Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children worldwide, with the most severe disease occurring in very young infants. Despite half a century of research there still are no licensed RSV vaccines. Difficulties in RSV vaccine development stem from a number of factors, including: (a) a very short time frame between birth and first RSV exposure; (b) interfering effects of maternal antibodies; and (c) differentially regulated immune responses in infants causing a marked T helper 2 (Th2) immune bias. This review seeks to provide an age-specific understanding of RSV immunity critical to the development of a successful pediatric RSV vaccine. Historical and future approaches to the prevention of infant RSV are reviewed, including passive protection using monoclonal antibodies or maternal immunization strategies versus active infant immunization using pre-fusion forms of RSV F protein antigens formulated with novel adjuvants such as Advax that avoid excess Th2 immune polarization.

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Maternal immunization with adjuvanted RSV prefusion F protein effectively protects offspring from RSV challenge and alters innate and T cell immunity

Cited by 10 publications

References 17 publications

Correlative outcomes of maternal immunization against RSV in cotton rats

Correlative outcomes of maternal immunization against RSV in cotton rats

Efficacy of maternal vaccination during pregnancy against infant respiratory viruses

Strategies for active and passive pediatric RSV immunization

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