Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates

Zohar, Tomer; Hsiao, Jeff C.; Mehta, Nickita; Das, Jishnu; Devadhasan, Anush; Karpinski, W; Callahan, Cheryl; Citron, Michael; DiStefano, Daniel J.; Touch, Sinoeun; Wen, Zhiping; Sachs, Jeffrey R.; Cejas, Pedro J.; Espeseth, Amy S.; Lauffenburger, Douglas A.; Bett, Andrew J.; Alter, Galit

doi:10.1016/j.chom.2021.11.006

Cited by 52 publications

(47 citation statements)

References 67 publications

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“…Interestingly, the mucosal vaccination provoked robust levels of F-specific antibodies in BAL fluids, while F- and G-specific humoral responses were rather low or undetectable in BAL samples of previously infected mice. F-specific IgA is an important correlate of protection against RSV in non-human primates ( 60 ) and in a human challenge study ( 6 ). The latter study reports an impaired induction of IgA + memory B cells after RSV infection, which is in line with our observations.…”

Section: Discussionmentioning

confidence: 99%

Mucosal immunization with an adenoviral vector vaccine confers superior protection against RSV compared to natural immunity

et al. 2022

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Respiratory syncytial virus (RSV) infections are the leading cause of severe respiratory illness in early infancy. Although the majority of children and adults mount immune responses against RSV, recurrent infections are frequent throughout life. Humoral and cellular responses contribute to an effective immunity but also their localization at respiratory mucosae is increasingly recognized as an important factor. In the present study, we evaluate a mucosal vaccine based on an adenoviral vector encoding for the RSV fusion protein (Ad-F), and we investigate two genetic adjuvant candidates that encode for Interleukin (IL)-1β and IFN-β promoter stimulator I (IPS-1), respectively. While vaccination with Ad-F alone was immunogenic, the inclusion of Ad-IL-1β increased F-specific mucosal immunoglobulin A (IgA) and tissue-resident memory T cells (TRM). Consequently, immunization with Ad-F led to some control of virus replication upon RSV infection, but Ad-F+Ad-IL-1β was the most effective vaccine strategy in limiting viral load and weight loss. Subsequently, we compared the Ad-F+Ad-IL-1β-induced immunity with that provoked by a primary RSV infection. Systemic F-specific antibody responses were higher in immunized than in previously infected mice. However, the primary infection provoked glycoprotein G-specific antibodies as well eventually leading to similar neutralization titers in both groups. In contrast, mucosal antibody levels were low after infection, whereas mucosal immunization raised robust F-specific responses including IgA. Similarly, vaccination generated F-specific TRM more efficiently compared to a primary RSV infection. Although the primary infection resulted in matrix protein 2 (M2)-specific T cells as well, they did not reach levels of F-specific immunity in the vaccinated group. Moreover, the infection-induced T cell response was less biased towards TRM compared to vaccine-induced immunity. Finally, our vaccine candidate provided superior protection against RSV infection compared to a primary infection as indicated by reduced weight loss, virus replication, and tissue damage. In conclusion, our mucosal vaccine candidate Ad-F+Ad-IL-1β elicits stronger mucosal immune responses and a more effective protection against RSV infection than natural immunity generated by a previous infection. Harnessing mucosal immune responses by next-generation vaccines is therefore a promising option to establish effective RSV immunity and thereby tackle a major cause of infant hospitalization.

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Section: Discussionmentioning

confidence: 99%

Mucosal immunization with an adenoviral vector vaccine confers superior protection against RSV compared to natural immunity

et al. 2022

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“…However, why similar levels of neutralization permit BA.2 to infect more efficiently than BA.1 may both be related to changes in the viral spike antigen( 25 ), but also related to compromised alternative antibody effector functions that may work synergistically with neutralization to promote full control of the virus at the mucosal barrier. Opsonophagocytic functions at the mucosal barrier are linked to protection against several infectious diseases including Streptococcus pneumoniae ( 26 ), RSV ( 27 ), Influenza ( 28 ), etc.. Moreover, Fc-effector functions may potentiate the immune-protective role of neutralizing antibodies, via a collaboration between the constant-domain (Fc) and antigen binding (Fab) domain of antibodies.…”

Section: Discussionmentioning

confidence: 99%

BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

Bartsch

Cizmeci

Kang

et al. 2022

Preprint

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The number of mutations in the omicron (B1.1.529) BA.1 variant of concern (VOC) led to an unprecedented evasion of vaccine induced immunity. However, despite the remarkable rise in global infections, severe disease and death did not increase proportionally, linked to persistent recognition of BA.1 by T cells and non-neutralizing opsonophagocytic antibodies. Yet, the emergence of a new sublineage, BA.2, that is more transmissible compared to BA.1, despite relatively preserved neutralizing antibody responses, has raised the possibility that BA.2 may evade other vaccine induced responses that may be key to protection against infection and disease. Here we comprehensively profiled the BNT162b2 vaccine induced response to several VOCs including the omicron BA.1 and BA.2, after the primary vaccine series, 8 months following vaccination, and after a boost. While vaccine induced immune responses were compromised against both Omicron sublineages, vaccine induced antibody isotype titers, FcγR3a- and FcγR3b-receptor binding levels, and non-neutralizing opsonophagocytic functions were significantly attenuated to the omicron BA.2 Spike compared to the BA.1 lineage. Conversely, FcγR2a and FcγR2b binding was elevated to BA.2 potentially contributing to persistent protection against severity of disease. These data point to an attenuation of particular non-neutralizing antibody properties that may be key to protection against transmission, but the maintenance of others that may continue to confer protection against disease.

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“…RSV infection is a major cause of bronchiolitis and pneumonia, especially in infants and young children [ 91 ]. After treatment of RSV-infected mice, a decrease in lung mucus was observed, accompanied by a significant decrease in the number of ILC2s and macrophages, and a decrease in IL-33 in bronchoalveolar lavage fluid [ 92 ].…”

Section: Crosstalk Between Ilc2s and Cd4 + T Cells...mentioning

confidence: 99%

Crosstalk between ILC2s and Th2 CD4+ T Cells in Lung Disease

Guo

2022

Journal of Immunology Research

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Cytokine secretion, such as interleukin-4 (IL-4), IL-5, IL-9, IL-13, and amphiregulin (Areg), by type 2 innate lymphoid cells (ILC2s) is indispensable for homeostasis, remodeling/repairing tissue structure, inflammation, and tumor immunity. Often viewed as the innate cell surrogate of T helper type 2 (Th2) cells, ILC2s not only secrete the same type 2 cytokines, but are also inextricably related to CD4+T cells in terms of cell origin and regulatory factors, bridging between innate and adaptive immunity. ILC2s interact with CD4+T cells to play a leading role in a variety of diseases through secretory factors. Here, we review the latest progress on ILC2s and CD4+T cells in the lung, the close relationship between the two, and their relevance in the lung disease and immunity. This literature review aids future research in pulmonary type 2 immune diseases and guides innovative treatment approaches for these diseases.

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Upper and lower respiratory tract correlates of protection against respiratory syncytial virus following vaccination of nonhuman primates

Cited by 52 publications

References 67 publications

Mucosal immunization with an adenoviral vector vaccine confers superior protection against RSV compared to natural immunity

Mucosal immunization with an adenoviral vector vaccine confers superior protection against RSV compared to natural immunity

BA.2 evasion of vaccine induced binding and functional non-neutralizing antibodies

Crosstalk between ILC2s and Th2 CD4+ T Cells in Lung Disease

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