tetano
Editor, Senior Moderator
Proc Natl Acad Sci U S A
. 2021 Aug 24;118(34):e2110714118.
doi: 10.1073/pnas.2110714118.
A recombinant herpes virus expressing influenza hemagglutinin confers protection and induces antibody-dependent cellular cytotoxicity
Katherine Kaugars[SUP] 1 [/SUP], Joseph Dardick[SUP] 1 [/SUP], Anna Paula de Oliveira[SUP] 1 [/SUP], Kayla A Weiss[SUP] 1 [/SUP], Regy Lukose[SUP] 1 [/SUP], John Kim[SUP] 1 [/SUP], Lawrence Leung[SUP] 1 [/SUP], Saranathan Rajagopalan[SUP] 1 [/SUP], Sydney Wolin[SUP] 1 [/SUP], Leor Akabas[SUP] 1 [/SUP], David M Knipe[SUP] 2 [/SUP], Goran Bajic[SUP] 3 [/SUP], William R Jacobs Jr[SUP] 4 [/SUP]
Affiliations
Abstract
Despite widespread yearly vaccination, influenza leads to significant morbidity and mortality across the globe. To make a more broadly protective influenza vaccine, it may be necessary to elicit antibodies that can activate effector functions in immune cells, such as antibody-dependent cellular cytotoxicity (ADCC). There is growing evidence supporting the necessity for ADCC in protection against influenza and herpes simplex virus (HSV), among other infectious diseases. An HSV-2 strain lacking the essential glycoprotein D (gD), was used to create ΔgD-2, which is a highly protective vaccine against lethal HSV-1 and HSV-2 infection in mice. It also elicits high levels of IgG2c antibodies that bind FcγRIV, a receptor that activates ADCC. To make an ADCC-eliciting influenza vaccine, we cloned the hemagglutinin (HA) gene from an H1N1 influenza A strain into the ΔgD-2 HSV vector. Vaccination with ΔgD-2::HA[SUB]PR8[/SUB] was protective against homologous influenza challenge and elicited an antibody response against HA that inhibits hemagglutination (HAI[SUP]+[/SUP]), is predominantly IgG2c, strongly activates FcγRIV, and protects against influenza challenge following passive immunization of naïve mice. Prior exposure of mice to HSV-1, HSV-2, or a replication-defective HSV-2 vaccine (dl5-29) does not reduce protection against influenza by ΔgD-2::HA[SUB]PR8[/SUB] This vaccine also continues to elicit protection against both HSV-1 and HSV-2, including high levels of IgG2c antibodies against HSV-2. Mice lacking the interferon-α/β receptor and mice lacking the interferon-γ receptor were also protected against influenza challenge by ΔgD-2::HA[SUB]PR8[/SUB] Our results suggest that ΔgD-2 can be used as a vaccine vector against other pathogens, while also eliciting protective anti-HSV immunity.
Keywords: ADCC; herpes simplex virus; influenza vaccine; viral vector.
. 2021 Aug 24;118(34):e2110714118.
doi: 10.1073/pnas.2110714118.
A recombinant herpes virus expressing influenza hemagglutinin confers protection and induces antibody-dependent cellular cytotoxicity
Katherine Kaugars[SUP] 1 [/SUP], Joseph Dardick[SUP] 1 [/SUP], Anna Paula de Oliveira[SUP] 1 [/SUP], Kayla A Weiss[SUP] 1 [/SUP], Regy Lukose[SUP] 1 [/SUP], John Kim[SUP] 1 [/SUP], Lawrence Leung[SUP] 1 [/SUP], Saranathan Rajagopalan[SUP] 1 [/SUP], Sydney Wolin[SUP] 1 [/SUP], Leor Akabas[SUP] 1 [/SUP], David M Knipe[SUP] 2 [/SUP], Goran Bajic[SUP] 3 [/SUP], William R Jacobs Jr[SUP] 4 [/SUP]
Affiliations
- PMID: 34417304
- DOI: 10.1073/pnas.2110714118
Abstract
Despite widespread yearly vaccination, influenza leads to significant morbidity and mortality across the globe. To make a more broadly protective influenza vaccine, it may be necessary to elicit antibodies that can activate effector functions in immune cells, such as antibody-dependent cellular cytotoxicity (ADCC). There is growing evidence supporting the necessity for ADCC in protection against influenza and herpes simplex virus (HSV), among other infectious diseases. An HSV-2 strain lacking the essential glycoprotein D (gD), was used to create ΔgD-2, which is a highly protective vaccine against lethal HSV-1 and HSV-2 infection in mice. It also elicits high levels of IgG2c antibodies that bind FcγRIV, a receptor that activates ADCC. To make an ADCC-eliciting influenza vaccine, we cloned the hemagglutinin (HA) gene from an H1N1 influenza A strain into the ΔgD-2 HSV vector. Vaccination with ΔgD-2::HA[SUB]PR8[/SUB] was protective against homologous influenza challenge and elicited an antibody response against HA that inhibits hemagglutination (HAI[SUP]+[/SUP]), is predominantly IgG2c, strongly activates FcγRIV, and protects against influenza challenge following passive immunization of naïve mice. Prior exposure of mice to HSV-1, HSV-2, or a replication-defective HSV-2 vaccine (dl5-29) does not reduce protection against influenza by ΔgD-2::HA[SUB]PR8[/SUB] This vaccine also continues to elicit protection against both HSV-1 and HSV-2, including high levels of IgG2c antibodies against HSV-2. Mice lacking the interferon-α/β receptor and mice lacking the interferon-γ receptor were also protected against influenza challenge by ΔgD-2::HA[SUB]PR8[/SUB] Our results suggest that ΔgD-2 can be used as a vaccine vector against other pathogens, while also eliciting protective anti-HSV immunity.
Keywords: ADCC; herpes simplex virus; influenza vaccine; viral vector.