Recently, India has been affected severely by a second wave of COVID-19 pandemic because of a newly emerged VOC (B.1.617.1) that exhibits potentially high infectivity and immune evasion ability. Compared to previously circulating SARS-CoV-2 variants, the B.1.617.1 variant contains multiple mutations in specific spike regions, including the N-terminal antigenic supersite, the receptor-binding domain (RBD), and the polybasic furin cleavage site at the S1/S2 boundary. Overall, this has raised a global concern as the B.1.617.1 variant has been identified in many countries outside India. A team of researchers in the U.S. recently conducted a study to examine whether natural infection-induced or vaccine-induced neutralizing antibodies are capable of eliminating the risk of recently emerged Indian variant (B.1.617.1) of SARS-CoV-2.
The findings reveal that sera obtained from convalescent individuals and those immunized with mRNA-based COVID-19 vaccines are capable of neutralizing the Indian variant, which has recently been categorized as the Variant of Concern (VOC) by the World Health Organization (WHO). In the current study, the scientists investigated whether serum samples obtained from SARS-CoV-2-infected or vaccinated individuals could neutralize the Indian VOC in live virus neutralization assays. For the live virus neutralization assay, serum samples were obtained from 24 COVID-19 recovered individuals and 25 vaccinated individuals. Of all vaccinated individuals, 15 received the Moderna COVID-19 vaccine, and 10 received the Pfizer/BioNTech vaccine. Specifically, the convalescent serum samples were collected after 31 to 91 days of symptom onset.
Similarly, the vaccinated serum samples were collected 35 – 51 days after the 2nd dose of Moderna vaccine and 7 – 27 days after the 2nd dose of Pfizer/BioNTech vaccine. The B.1.617.1 variant of SARS-CoV-2 was isolated from the residual mid turbinate swab sample of a COVID-19 patient in Stanford, California. Compared to wildtype SARS-CoV-2, the B.1.617.1 variant showed lower sensitivity to neutralization by the serum samples obtained from both convalescent and vaccinated individuals. Specifically, the convalescent serum samples exhibited the average neutralizing antibody titers of 514 and 79 against the wildtype virus and the B.1.617.1 variant, respectively. However, the neutralizing antibody titers against the variant could not be detected in 5 convalescent serum samples.
The serum samples obtained from Moderna-vaccinated individuals showed the average neutralizing antibody titers of 1332 and 190 against the wildtype virus and the B.1.617.1 variant, respectively. Similarly, the Pfizer/BioNTech-vaccinated serum samples exhibited the average antibody titers of 1176 and 164 against the wildtype virus and the variant, respectively. The study findings indicate that compared to the wildtype virus, the B.1.617.1 variant is significantly resistant (6.8-fold) to neutralization by antibodies developed in response to natural infection or vaccination. Despite such lower sensitivity, about 79% of convalescent sera and 100% of vaccinated sera showed considerable effectiveness in neutralizing the B.1.617.1 variant. Taken together, the study highlights the effectiveness of COVID-19 vaccines in inducing neutralizing antibodies against SARS-CoV-2 variants.
In another study, an indipendent team of scientists from the Washington University School of Medicine and the University of Texas Medical Branch, USA, has evaluated the durability and robustness of an adenovirus-vectored, spike-based intranasal coronavirus disease 2019 (COVID-19) vaccine in mice. Their analyses reveal that a single dose of the vaccine is capable of inducing both neutralizing and binding antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants for a prolonged time period. Previous studies ACE2-expressing transgenic mice, hamsters, and non-human primates have shown that this vaccine is capable of inducing strong antibody-mediated, cell-mediated, and mucosal immune responses. The vaccine is currently under investigation in human clinal trials.
For the study purpose, mice were administered with different doses of the vaccine via the intramuscular or intranasal route. Afterward, the mice were intranasally infected with SARS-CoV-2 or its variants. For various virological assays, the serum and tissue samples were collected from vaccinated mice. To evaluate the vaccine efficacy vaccinated sera were analyzed for anti-spike binding and neutralizing antibodies. In addition, bone marrow samples collected from vaccinated mice were analyzed for spike-specific IgG- and IgA-secreting plasma cells. The measurement of serum anti-spike and anti-receptor binding domain (RBD) antibody titers by ELISA revealed that a single dose of intranasally injected vaccine induces significantly higher IgG-specific binding antibodies than intramuscularly injected vaccine after 100 and 200 days of vaccination.
In contrast to intramuscularly immunized mice that did not exhibit IgA-specific immunity, significantly higher titers of IgA-specific binding antibodies were observed in mice immunized intranasally. These findings indicate that an intranasal route of vaccine administration is superior to the intramuscular route in inducing strong and long-lasting IgG- and IgA-specific anti-SARS-CoV-2 antibody responses in serum. Regarding antibody responses against different spike and RBD mutations observed in SARS-CoV-2 variants (B.1.1.7, B.1.351, and B.1.1.28 lineages), the findings revealed that the vaccine administered via intranasal route is capable of inducing higher antibody responses against all tested variants of spike and RBD compared to the intramuscularly injected vaccine.
The measurement of bone marrow-derived long-lived plasma cells at 200-day post-vaccination revealed 4-fold higher levels of spike-specific IgG- and IgA-secreting long-lived plasma cells in intranasally immunized mice than intramuscularly immunized mice. The serum samples collected from mice after 6 weeks and 9 months of intranasal vaccination showed high levels of binding and neutralizing antibodies against wildtype SARS-CoV-2. However, a 3-fold to 8-fold reduction in neutralizing ability was observed against SARS-CoV-2 variants. Importantly, in mice infected with wildtype virus or SARS-CoV-2 variants after 9 months of intranasal vaccination, significantly lower levels of viral RNA were observed in the upper and lower respiratory tracts, heart, and brain.
Beside the immmunological advantages unveiled by the research, the interesting point is the superior effecetiveness of the anasal route compared to the usual intramuscular like vaccines as we know them. It would be better to spray a dose like a flu reliever, than getting a sting in the arm, would it?
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Edara VV et al. bioRxiv May 9: 443299v1.
Hassan N et al. bioRxiv May 8: 443267v1.
Srivastava et al. Front Immunol 2021; 12:637982.
Dott. Gianfrancesco Cormaci
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