A recombinant herpes virus expressing influenza hemagglutinin confers protection and induces antibody-dependent cellular cytotoxicity

Abstract

Significance Despite decades of research, we lack an effective vaccine against influenza, a deadly virus that costs the United States nearly $90 billion annually. Current strategies do not translate into highly protective immunity against circulating and novel influenza strains. Here, we demonstrate that a herpes simplex viral (HSV) vector expressing hemagglutinin can be used to elicit a protective response against influenza. The efficacy of this vector is not abrogated by preexisting immunity to HSV, protects against lethal HSV challenge, and elicits highly functional FcγRIV-binding antibodies that can activate immune cell effector function. Expanding the use of ΔgD-2 as a viral vector in general could generate vaccines that are highly protective, quickly synthesized, and simultaneously effective against multiple pathogens.

Going above and Beyond: Using an Attenuated Herpes Viral Vaccine Vector to Elicit Protective Immune Responses Through Neutralizing and Non-neutralizing Functions of Antibodies

“…This vaccine also elicited IgG2c antibodies against HSV, similar to the parental vector [55]. The immunized sera had high titers in the hemagglutination inhibition assay, a well-established proxy for neutralizing titer for influenza vaccines [55]. To both probe immunological mechanisms and establish the potential study of other viral infections requiring immunodeficient mouse models with this vector, we tested our vector in mice without functional type I and II IFNs, specifically IFN-α/β (IFNAR -/-) and IFN-γ receptor-deficient (IFNγR -/-) mice, respectively [55].…”

“…We found that this vaccine specifically elicited high levels of FcγRIV-activating IgG2c antibodies against the influenza HA protein encoded within the recombinant virus and not influenza strains with other HAs. This vaccine also elicited IgG2c antibodies against HSV, similar to the parental vector [55]. The immunized sera had high titers in the hemagglutination inhibition assay, a well-established proxy for neutralizing titer for influenza vaccines [55].…”

“…In Kaugars et al, 2021, we introduced a vaccine, ΔgD-2::HA PR8 , that is protective against influenza and HSV during in vivo challenge [55]. To create ΔgD-2::HA PR8 , we inserted the gene for HA from an H1N1 strain of influenza into ΔgD-2 [55].…”

“…In Kaugars et al, 2021, we introduced a vaccine, ΔgD-2::HA PR8 , that is protective against influenza and HSV during in vivo challenge [55]. To create ΔgD-2::HA PR8 , we inserted the gene for HA from an H1N1 strain of influenza into ΔgD-2 [55]. We found that this vaccine specifically elicited high levels of FcγRIV-activating IgG2c antibodies against the influenza HA protein encoded within the recombinant virus and not influenza strains with other HAs.…”

Capturing Structural Variants of Herpes Simplex Virus Genome in Full Length by Oxford Nanopore Sequencing

“…We recently developed a method to extract intact full-length genomic DNA from HSV-1 and HSV-2, followed by sequencing and capturing their genome as a single read by ONT. Genomic DNA from HSV-1 clinical strain (B 3 x 1.1) ( 18 ) was isolated following the protocol optimized earlier ( 19 ). Briefly, Vero cells were infected at a multiplicity of infection (MOI) of 10 −2 PFU/cell for 1 h at 37°C.…”