scholarly journals Detection of persistent SARS-CoV-2 IgG antibodies in oral mucosal fluid and upper respiratory tract specimens following COVID-19 mRNA vaccination

Author(s):  
Aubree Mades ◽  
Prithivi Chellamuthu ◽  
Lauren Lopez ◽  
Noah Kojima ◽  
Melanie A MacMullan ◽  
...  

Previous studies have shown that mRNA COVID-19 vaccines are highly effective at preventing SAR-CoV-2 infection by generating an immune response, which in part produces SARS-CoV-2 IgG antibodies in serum. In this study, we hypothesized that COVID-19 vaccines may elicit production of SARS-CoV-2 IgG antibodies in the upper respiratory tract, such as in oral and nasal mucosal fluid. To test that hypothesis, we enrolled 114 participants within 3-7 days of receiving the first dose of the Moderna mRNA COVID-19 vaccine and collected oral mucosal fluid samples on days 5, 10, 15, and 20 after each vaccine dose. Of participants naive to SARS-CoV-2 (n = 89), 79 (85.4%) tested positive for SARS-CoV-2 IgG antibodies by time point 2 (10 days +/-2 days after first vaccine dose), and 100% tested positive for SARS-CoV-2 IgG by time point 3 (15 days +/- 2 days after first vaccine dose). Additionally, we collected paired oral mucosal fluid and anterior nares samples from 10 participants who had received both vaccine doses. We found that participants had an average SARS-CoV-2 IgG antibody concentration of 2496.0 +/- 2698.0ng/mL in nasal mucosal fluid versus 153.4 +/- 141.0ng/mL in oral mucosal fluid. Here, we demonstrate detection and longitudinal persistence of SARS-CoV-2 IgG antibodies in upper respiratory tract specimens following COVID-19 mRNA vaccination. A high concentration of IgG targeting viral spike protein in the upper respiratory system may play an unexplored role in the prevention of SARS-CoV-2 infection and deserves further investigation.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aubree Mades ◽  
Prithivi Chellamathu ◽  
Noah Kojima ◽  
Lauren Lopez ◽  
Melanie A. MacMullan ◽  
...  

AbstractCOVID-19 mRNA vaccines are highly effective at preventing COVID-19. Prior studies have found detectable SARS-CoV-2 IgG antibodies in oral mucosal specimens of participants with history of COVID-19. To assess the development of oral SARS-CoV-2 IgG antibodies among people who received either the Moderna or Pfizer/BioNTech COVID-19 vaccination series, we developed a novel SARS-CoV-2 IgG enzyme-linked immunosorbent assay (ELISA) to quantify the concentrations of oral and nasal mucosal SARS-CoV-2 IgG levels. We enrolled 52 participants who received the Moderna vaccine and 80 participants who received the Pfizer/BioNTech vaccine. Oral mucosal specimens were self-collected by participants prior to or on the day of vaccination, and on days 5, 10, 15, and 20 following each vaccination dose and 30, 60, and 90 days following the second vaccination dose. A subset of the cohort provided additional nasal mucosal specimens at every time point. All participants developed detectable oral mucosal SARS-CoV-2 IgG antibodies by 15 days after the first vaccination dose. There were no significant differences in oral mucosal antibody concentrations once participants were fully vaccinated in the Moderna and Pfizer/BioNTech vaccines. Oral or nasal mucosal antibody testing could be an inexpensive and less invasive alternative to serum antibody testing. Further research is needed to understand the duration of detectable oral or nasal mucosal antibodies and how antibody concentrations change with time.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Huibi Cao ◽  
Juntao Mai ◽  
Zhichang Zhou ◽  
Zhijie Li ◽  
Rongqi Duan ◽  
...  

Abstract Background The ongoing COVID-19 pandemic has resulted in 185 million recorded cases and over 4 million deaths worldwide. Several COVID-19 vaccines have been approved for emergency use in humans and are being used in many countries. However, all the approved vaccines are administered by intramuscular injection and this may not prevent upper airway infection or viral transmission. Results Here, we describe a novel, intranasally delivered COVID-19 vaccine based on a helper-dependent adenoviral (HD-Ad) vector. The vaccine (HD-Ad_RBD) produces a soluble secreted form of the receptor binding domain (RBD) of the SARS-CoV-2 spike protein and we show it induced robust mucosal and systemic immunity. Moreover, intranasal immunization of K18-hACE2 mice with HD-Ad_RBD using a prime-boost regimen, resulted in complete protection of the upper respiratory tract against SARS-CoV-2 infection. Conclusion Our approaches provide a powerful platform for constructing highly effective vaccines targeting SARS-CoV-2 and its emerging variants.


2021 ◽  
Author(s):  
Joan E.M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  

Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1x109 vp and 1x1010 vp elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers which was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these pre-clinical data confirm efficacy of a 1-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.


npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Joan E. M. van der Lubbe ◽  
Sietske K. Rosendahl Huber ◽  
Aneesh Vijayan ◽  
Liesbeth Dekking ◽  
Ella van Huizen ◽  
...  

AbstractPreviously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.


Hygiene ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 1-11
Author(s):  
Günter Kampf

Fundamental rights are probably given back earlier to COVID-19 vaccinated individuals assuming that they cannot spread SARS-CoV-2 anymore. The objective of the study was to determine if COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission. PubMed was searched for studies on 4 April 2021. All studies with original data on COVID-19 cases among vaccinated individuals (phase III RCTs) and on viral load in the upper respiratory tract of vaccinated macaques after a SARS-CoV-2 challenge were included. Symptomatic COVID-19 cases were found in four trials among vaccinated participants although less frequently than among control subjects. One study revealed asymptomatic COVID-19 cases in a similar frequency among 2.168 AZD1222-vaccinated subjects (1.0%) compared to 2.223 control subjects (1.0%). In 15 studies with vaccinated macaques, it was found that the load of SARS-CoV-2 RNA, subgenomic RNA and infectious virus in the upper respiratory tract is variable. Sterilizing immunity was found in none of the animal studies. Major limitations of the animal studies are that the SARS-CoV-2 challenge took place within a few weeks of the final or only vaccine dose, that the viral challenge was often high and, in some studies, administered by up to four routes. Based on current knowledge it seems clear that COVID-19 vaccinated individuals can still be the source of SARS-CoV-2 transmission.


1999 ◽  
Vol 67 (6) ◽  
pp. 2884-2890 ◽  
Author(s):  
Anna Rudin ◽  
Gerdt C. Riise ◽  
Jan Holmgren

ABSTRACT Nasal vaccine delivery is superior to oral delivery in inducing specific immunoglobulin A (IgA) and IgG antibody responses in the upper respiratory tract. Although an antibody response in the nasal passages is important in protecting against primary colonization with lung pathogens, antibodies in the lungs are usually required as well. We immunized 15 male volunteers twice nasally or orally with cholera toxin B subunit (CTB) and determined the specific antibody levels in serum, bronchoalveolar lavage (BAL) fluid, and urine before and 2 weeks after immunization. Nasal immunization induced fivefold increases in the levels of specific IgA antibodies in BAL fluid of most volunteers, whereas there were no significant specific IgA responses after oral immunization. The specific IgG antibody level increased eightfold in BAL fluid in the nasally vaccinated subjects, and the major part of IgG had most probably been transferred from serum. Since the specific IgG response in serum was lower in the individuals vaccinated orally, the IgG response in BAL fluid in this group was also lower and not significant. In conclusion, nasal immunization is also preferable to the oral route when vaccinating against lower respiratory tract infections, and a systemic immune response is considerably more important in the lower than in the upper respiratory tract. Moreover, both nasal and oral immunizations were able to stimulate 6- to 10-fold specific IgA and IgG responses in urine in about half of the individuals, which indicates that distant mucosal vaccination might be used to prevent adhesion of pathogens to the urogenital tract.


2021 ◽  
Author(s):  
Rana Abdelnabi ◽  
Caroline Shi-Yan Foo ◽  
Xin Zhang ◽  
Viktor Lemmens ◽  
Piet Maes ◽  
...  

The emergence of SARS-CoV-2 variants of concern (VoCs) has exacerbated the COVID-19 pandemic. End of November 2021, a new SARS-CoV-2 variant namely the omicron (B.1.1.529) emerged. Since this omicron variant is heavily mutated in the spike protein, WHO classified this variant as the 5th variant of concern (VoC). We previously demonstrated that the other SARS-CoV-2 VoCs replicate efficiently in Syrian hamsters, alike also the ancestral strains. We here wanted to explore the infectivity of the omicron variant in comparison to the ancestral D614G strain. Strikingly, in hamsters that had been infected with the omicron variant, a 3 log10 lower viral RNA load was detected in the lungs as compared to animals infected with D614G and no infectious virus was detectable in this organ. Moreover, histopathological examination of the lungs from omicron-infecetd hamsters revealed no signs of peri-bronchial inflammation or bronchopneumonia. Further experiments are needed to determine whether the omicron VoC replicates possibly more efficiently in the upper respiratory tract of hamsters than in their lungs.


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