Delayed virus‐specific antibody responses associate with COVID‐19 mortality

The potential of a pseudorabies virus (PRV) nucleocapsid protein (NC)-based enzyme-linked immunosorbent assay (ELISA) as a screening assay for PRV infection in subunit-vaccinated and nonvaccinated pigs was studied. The NC-ELISA compared favorably to a commercial ELISA for detecting PRV infection in nonvaccinated pigs. Virus-specific antibody was first detected by the NC-ELISA between days 14 and 21 in 5 pigs challenged intranasally with 104PFU of virus. Antibody continued to be detected in these pigs through day 42, when the experiment was terminated. The NC-ELISA also detected antibody in 23 of 24 pigs from PRV-infected herds. In contrast, the commercial ELISA detected antibody 1 week earlier than the NC-ELISA in experimentally infected pigs but failed to detect antibody in 3 naturally exposed pigs that were identified by the NC-ELISA. Infection in these animals was confirmed by radioimmunoprecipitation analysis. The potential usefulness of the NC-ELISA for detecting infection in vaccinated pigs was also evaluated. The nucleocapsid-specific antibody responses of 10 PRV envelope glycoprotein subunit-vaccinated pigs were monitored prior to and following nasal exposure to a low dose (1023PFU) of PRV. Sera were collected periodically for 113 days after infection. Nucleocapsid-specific antibody responses measured by the NC-ELISA remained below the positive threshold before challenge but increased dramatically following virus exposure. Maximum ELISA responses were obtained on day 32 postchallenge (p.c.). Mean ELISA responses decreased thereafter but remained well above the positive threshold on day 113 p.c. PRV nucleocapsid protein can be used effectively as antigen in the ELISA for detecting PRV infection in both nonvaccinated and subunit-vaccinated pigs.

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A Multiagent Alphavirus DNA Vaccine Delivered by Intramuscular Electroporation Elicits Robust and Durable Virus-Specific Immune Responses in Mice and Rabbits and Completely Protects Mice against Lethal Venezuelan, Western, and Eastern Equine Encephalitis Virus Aerosol Challenges

Journal of Immunology Research ◽

10.1155/2018/8521060 ◽

2018 ◽

Vol 2018 ◽

pp. 1-15 ◽

Cited By ~ 3

Author(s):

Lesley C. Dupuy ◽

Michelle J. Richards ◽

Brian D. Livingston ◽

Drew Hannaman ◽

Connie S. Schmaljohn

Keyword(s):

Dna Vaccine ◽

Specific Antibody ◽

Dna Vaccines ◽

Protective Efficacy ◽

Effective Means ◽

Encephalitis Virus ◽

Antibody Responses ◽

Equine Encephalitis Virus ◽

Virus Specific Antibody ◽

The Individual

There remains a need for vaccines that can safely and effectively protect against the biological threat agents Venezuelan (VEEV), western (WEEV), and eastern (EEEV) equine encephalitis virus. Previously, we demonstrated that a VEEV DNA vaccine that was optimized for increased antigen expression and delivered by intramuscular (IM) electroporation (EP) elicited robust and durable virus-specific antibody responses in multiple animal species and provided complete protection against VEEV aerosol challenge in mice and nonhuman primates. Here, we performed a comparative evaluation of the immunogenicity and protective efficacy of individual optimized VEEV, WEEV, and EEEV DNA vaccines with that of a 1 : 1 : 1 mixture of these vaccines, which we have termed the 3-EEV DNA vaccine, when delivered by IM EP. The individual DNA vaccines and the 3-EEV DNA vaccine elicited robust and durable virus-specific antibody responses in mice and rabbits and completely protected mice from homologous VEEV, WEEV, and EEEV aerosol challenges. Taken together, the results from these studies demonstrate that the individual VEEV, WEEV, and EEEV DNA vaccines and the 3-EEV DNA vaccine delivered by IM EP provide an effective means of eliciting protection against lethal encephalitic alphavirus infections in a murine model and represent viable next-generation vaccine candidates that warrant further development.

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Rift Valley Fever Virus Clearance and Protection from Neurologic Disease Are Dependent on CD4+ T Cell and Virus-Specific Antibody Responses

Journal of Virology ◽

10.1128/jvi.00337-13 ◽

2013 ◽

Vol 87 (11) ◽

pp. 6161-6171 ◽

Cited By ~ 22

Author(s):

K. A. Dodd ◽

A. K. McElroy ◽

M. E. B. Jones ◽

S. T. Nichol ◽

C. F. Spiropoulou

Keyword(s):

Specific Antibody ◽

Rift Valley ◽

Rift Valley Fever ◽

Rift Valley Fever Virus ◽

Antibody Responses ◽

Cd4 T Cell ◽

Neurologic Disease ◽

Valley Fever ◽

Virus Clearance ◽

Virus Specific Antibody

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Novel, Chimpanzee Serotype 68-Based Adenoviral Vaccine Carrier for Induction of Antibodies to a Transgene Product

Journal of Virology ◽

10.1128/jvi.76.6.2667-2675.2002 ◽

2002 ◽

Vol 76 (6) ◽

pp. 2667-2675 ◽

Cited By ~ 142

Author(s):

Zhiquan Xiang ◽

Guangping Gao ◽

Arturo Reyes-Sandoval ◽

Christopher J. Cohen ◽

Yan Li ◽

...

Keyword(s):

Antibody Response ◽

Rabies Virus ◽

Specific Antibody ◽

Lethal Dose ◽

Antibody Responses ◽

Distinct Advantage ◽

Rabies Virus Glycoprotein ◽

Virus Glycoprotein ◽

Virus Specific Antibody ◽

Vaccine Carrier

ABSTRACT An E1-deletion-containing adenoviral recombinant based on the chimpanzee serotype 68 (AdC68) was developed to express the rabies virus glycoprotein. Mice immunized with this construct (AdC68rab.gp) developed antibodies to rabies virus and remained resistant to challenge with an otherwise lethal dose of rabies virus. In naïve mice immunized intranasally, the rabies virus-specific antibody responses elicited by AdC68rab.gp were comparable with regard to both titers and isotype profiles to those induced by an adenoviral recombinant based on human serotype 5 (Adhu5) expressing the same transgene product. In contrast, subcutaneous immunization with the AdC68rab.gp vaccine resulted in markedly lower antibody responses to the rabies virus glycoprotein than the corresponding Adhu5 vaccine. Antibodies from AdC68rab.gp-immunized mice were strongly biased towards the immunoglobulin G2a isotype. The antibody response to the rabies virus glycoprotein presented by Adhu5rab.gp was severely compromised in animals preexposed to the homologous adenovirus. In contrast, the rabies virus-specific antibody response to the AdC68rab.gp vaccine was at most marginally affected by preexisting immunity to common human adenovirus serotypes, such as 2, 4, 5, 7, and 12. This novel vaccine carrier thus offers a distinct advantage over adenoviral vaccines based on common human serotypes.

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SARS-CoV-2 naïve and recovered individuals show qualitatively different antibody responses following mRNA vaccination

10.1101/2021.05.07.21256821 ◽

2021 ◽

Author(s):

Sonia Tejedor Vaquero ◽

Leire de Campos-Mata ◽

José María Ramada ◽

Pilar Díaz ◽

Juan Navarro-Barriuso ◽

...

Keyword(s):

Specific Antibody ◽

Natural Infection ◽

Neutralizing Antibody ◽

Primary Vaccination ◽

Antibody Responses ◽

Specific Antibody Response ◽

Vaccination Programs ◽

Virus Specific Antibody ◽

Compositional Patterns ◽

Humoral Responses

mRNA-based vaccines effectively induce protective neutralizing antibody responses against SARS-CoV-2, the etiological agent of COVID-19. The specific compositional patterns of these responses remain largely unknown. We found that SARS-CoV-2-naïve individuals receiving the first dose of an mRNA vaccine developed a SARS-CoV-2-specific antibody response with a subclass profile comparable to that induced by the natural infection, except IgA2, which did not increase. SARS-CoV-2-naïve subjects also mounted a robust virus-specific recall response after receiving the second dose. This response increased all IgG subclasses, but boosted neither IgM nor IgA1 and IgA2 subclasses. In contrast, individuals recovered from COVID-19 mounted peak virus-specific antibody responses upon primary immunization and did not further augment such responses following secondary immunization. Remarkably, compared to SARS-CoV-2-naïve subjects, individuals with pre-existing immunity showed increased levels of all virus-specific antibodies but IgG3 following primary vaccination. By dissecting the heterogeneity of mRNA vaccine-induced humoral responses to SARS-CoV-2, our findings indicate that the induction of optimal immune protection may require the development of personalized vaccination programs.

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