Can antibody tests determine if the COVID-19 vaccine was effective?
The Centers for Disease Control and Prevention (CDC) discourages antibody testing for assessing immunity after getting the vaccine.
A vaccinated person is very likely to get a negative result from a serology test, even if the vaccine was successful and protective. That’s because different serology tests detect antibodies to different parts of the virus.
Some tests detect antibodies to the spike protein of the virus, which are produced in response to viral infection or the vaccine. Others detect antibodies to a different part of the virus called the nucleocapsid protein, which are produced in response to infection, but not by the current vaccines.
MD Anderson’s Blood Bank uses an antibody test designed to detect antibodies to the nucleocapsid protein, which means donors who have received the COVID-19 vaccine will likely receive a negative antibody test result.
“A vaccinated person should not be alarmed or worried if they receive a negative antibody test result because this test does not detect antibodies from the Pfizer, Moderna and Johnson & Johnson’s Janssen COVID-19 vaccines, which were developed against the spike protein of the virus,” says Fernando Martinez, M.D., medical director of Laboratory Medicine. “This reinforces the guidance from the CDC that serology tests should not be used to test for immunity.”
Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 Coronavirus
Front. Immunol., 30 October 2020
Isabel Kinney Ferreira de Miranda Santos1* and Carlos Henrique Nery Costa2 1Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil 2Nathan Portela Institute of Tropical Medicine, Federal University of Piauí, Teresina, Brazil • Humoral immunity is a crucial aspect in mitigating the COVID-19 pandemic.
• Hydroxychloroquine and chloroquine are lysosomotropic drugs that affect antigen-presenting pathways and B-cell activation.
• Chloroquine inhibits antibody responses to vaccines, but reports about this effect apparently have not been called to the attention of investigators in the field of COVID-19.
• Studies on immunity to Sars-CoV-2 must take into account treatment regimens for COVID-19.
Introduction Recent large observational studies indicate that hydroxychloroquine (HY) does not affect outcomes of patients hospitalized with COVID-19 (1, 2) and may even be harmful (3). Results of double-blind, randomized studies to assess efficacy of HY more rigorously are still not available. In spite of these facts, officials are currently advocating use of hydroxychloroquine (HY) for treatment and even prevention of COVID-19. In view of this situation and of the importance of correct interpretation of antibody profiles for planning preventive measures for COVID-19, we would like to bring the attention of readers to studies that raise concerns about the possible impact of HY upon antibody responses to SARS-CoV-2.
Impact of Chloroquine and Derivatives on Responses to Vaccines and Antigen Presentation In 1986, Pappaionaou et al. (4) recalled the tragic story of a Peace Corps worker in Kenya who succumbed to rabies after being bitten by her rabies-infected pet dog despite having received a full regimen of human diploid-cells rabies vaccine 6 months prior to the bite. The subject had been vaccinated while receiving chloroquine as prophylaxis for malaria. Prompted by this finding, Pappaionaou et al. carried out a randomized controlled trial that showed that chloroquine suppressed antibody responses to the rabies vaccine (4). Subsequently, Fryauff et al. demonstrated a similar effect of chloroquine, but not of primaquine, on antibody responses to tetanus and diphtheria vaccines (5). More recently, Endy et al. showed that antibody responses of individuals vaccinated with a purified chick embryo cell rabies vaccine, given on a postexposure prophylaxis schedule, were significantly lower in individuals receiving chloroquine compared with controls (6).
HY and chloroquine are lysosomotropic drugs that increase the pH of the lysosome, thus affecting functions of proteins involved in antigen presenting pathways and in B-cell activation (7). To the best of our knowledge, there are no new facts in the scientific and medical literature that indicate that the same mechanism could not operate in HY-treated patients suffering from COVID-19 and negatively impact their SARS-CoV-2-specific antibody responses. Indeed, recent findings indicate that some individuals, including hospitalized patients, who have recovered from COVID-19 have not made vigorous IgG antibody responses. However, the most comprehensive publications addressing antibody responses, wherein study subjects presented viability in levels of IgG antibody responses, have not detailed the treatment regimens delivered to the subjects (8–11).
Discussion Plans for employing immunity profiles against SARS-CoV-2 to relax social distancing and other epidemic mitigation measures and to create “immunity passports” to control spread of COVID-19 have recently been questioned by the World Health Organization because of uncertainty regarding antibody responses (12). As more needs to be learned about the role of antibodies in recovery from and protection against infection with SARS-CoV-2, the impact of HY and other treatment regimens on antibody responses requires systematic evaluation.
Author Contributions All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
Funding This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant Number 2020/09093-5 to IM).
Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Background: Chloroquine can impair the immune responses to intradermal rabies vaccination. Current guidelines recommend an extra intramuscular dose be given for postexposure prophylaxis in previously unvaccinated persons taking any antimalarial drug.
Methods: We conducted a randomized, open-label, single-site study in 103 previously unvaccinated healthy adults age ≥18 to ≤60 years old to evaluate the effects of chloroquine, atovaquone/proguanil (Malarone), and doxycycline on the antibody response to a purified chick embryo cell vaccine, given on a postexposure prophylaxis schedule. All treatment groups received antimalarials 14 days prior to and during vaccination.
Results: All subjects achieved accepted neutralizing antibody titers of ≥0.5 IU/mL following the second rabies vaccination dose and maintained this protection through the duration of the study. We observed a reduction in rabies antibody geometric mean titer in the chloroquine versus control groups 28 days after vaccination: 2.3 versus 6.87 IU/mL, respectively (P < .001, t test). A significant difference was not observed for those taking Malarone or doxycycline.
Conclusions: We conclude that there is no reduction of rabies antibody response in subjects taking Malarone or doxycycline, but a significant reduction in those taking chloroquine; however, accepted antibody levels were achieved for all 3 antimalarials.
如今，随着加拿大疫苗的普及，距离未来解封的日子也越来越近了，可如果你注射的疫苗，并没有产生抗体怎么办?
据美国密歇根研究小组发现，如果你正在服用一些特定的药品，就会削弱你自身的免疫系统，直接导致新冠疫苗无法生效。
赶紧自查，最近有没有接受过以下治疗，或服用以下药品：
1、治疗癌症和自身免疫性疾病，比如多发性硬化症、风湿关节炎、狼疮、克罗恩病(某种肠道炎)等。
2、因为关节炎、肠道炎等服用了某些药物的就要特别留意了，这些药可能会抑制产生抗体，如果已经约好新冠疫苗接种，最好先咨询一下医生的意见。
免疫力弱化药物
导致美国至少9万人疫苗失效
据美国密歇根小组的研究，分析了320万私人保险患者数据，大概有3%的人，也就是9万名美国人，服用了化学疗法，类似于类固醇和其他免疫抑制药物。他们自身对于疫苗的反应很慢很弱，甚至没有反应。
而这个数据只是其中一部分，还有一些保险以外的人群，应该波及到的人更多。
目前，加拿大第一针的接种率与美国非常接近，共有48.179%的国民接种完首针。但接种完疫苗并不意味着就一定会产生抗体受到保护！
如果一些人不能产生抗体，等于就算75%的人已经接种，也不意味着75%的人都得到了免疫…真正的群体免疫，依然难以实现。
多伦多大学传染病诊所负责人Deepali Kumart博士表示：“我们知道在免疫抑制人群中，他们接种新冠疫苗后产生的抗体会比普通人群低。我们暂时无法知道这些人注射疫苗后能产生多少抗体。”
目前，疫情还不能松懈，前日宣布解封计划的安省在病例连续下降两天后出现反弹，昨日又报告新增2400例，死亡27人。变种病例持续增加，其中英国变种病例已累计114,569例，比前天1天就增加1810例。
在这种情况下，如果疫苗的作用不能发挥到最大化，也是很可怕的现象！
所以，如果你或者身边的家人，接受过上述治疗，并服用过一些治疗关节炎、肠道炎等药物的，就一定要注意多加防范，已经预约过疫苗的也要即使与医生联系，把自身的情况详细告知，听取医生的意见。
https://www.dailymail.co.uk/health/article-9600671/Covid-vaccines-not-work-90K-Americans-immune-drugs.html
breakthrough cases的一大原因。这些人只能依靠别人打疫苗产生的群体免疫来保护。
打过疫苗的一般测IgG抗体（抗S蛋白的），目的是看是否产生了免疫力。得过新冠的主要测IgM抗体（抗N蛋白的），目的是确定是否最近得过新冠。当然，得过新冠的也可以测IgG抗体，看是否产生了免疫力。
https://www.news-medical.net/news/20210421/Antibody-response-induced-by-mRNA-vaccination-differs-from-natural-SARS-CoV-2-infection.aspx
https://www.mdanderson.org/cancerwise/what-do-negative-positive-antibody-test-results-mean-after-a-covid-19-vaccine.h00-159459267.html
Can antibody tests determine if the COVID-19 vaccine was effective?
The Centers for Disease Control and Prevention (CDC) discourages antibody testing for assessing immunity after getting the vaccine.
A vaccinated person is very likely to get a negative result from a serology test, even if the vaccine was successful and protective. That’s because different serology tests detect antibodies to different parts of the virus.
Some tests detect antibodies to the spike protein of the virus, which are produced in response to viral infection or the vaccine. Others detect antibodies to a different part of the virus called the nucleocapsid protein, which are produced in response to infection, but not by the current vaccines.
MD Anderson’s Blood Bank uses an antibody test designed to detect antibodies to the nucleocapsid protein, which means donors who have received the COVID-19 vaccine will likely receive a negative antibody test result.
“A vaccinated person should not be alarmed or worried if they receive a negative antibody test result because this test does not detect antibodies from the Pfizer, Moderna and Johnson & Johnson’s Janssen COVID-19 vaccines, which were developed against the spike protein of the virus,” says Fernando Martinez, M.D., medical director of Laboratory Medicine. “This reinforces the guidance from the CDC that serology tests should not be used to test for immunity.”
加一篇FDA官网： https://www.fda.gov/news-events/press-announcements/fda-brief-fda-advises-against-use-sars-cov-2-antibody-test-results-evaluate-immunity-or-protection
包括目前抗体检测技术及标准的改进和完善。 换位思考，不管处在CDC还是FDA立场角度，他们讲话都不能把话说绝/说死。
在1986年发现，肯尼亚人被携带狂犬病的宠物咬伤后，完整疫苗却没有发挥出应有的作用，就是因为患者使用过防治疟疾的氯喹。
受到这个病例的启发，这位医生进行了随机对照试验，发现：氯喹抑制狂犬疫苗的抗体反应。随后其他几位医生也发现氯喹对破伤风，白喉疫苗也有类似的抑制反应。
Impact of Hydroxychloroquine on Antibody Responses to the SARS-CoV-2 CoronavirusFront. Immunol., 30 October 2020
Isabel Kinney Ferreira de Miranda Santos1* and Carlos Henrique Nery Costa2
1Ribeirão Preto School of Medicine, University of São Paulo, São Paulo, Brazil
2Nathan Portela Institute of Tropical Medicine, Federal University of Piauí, Teresina, Brazil
• Humoral immunity is a crucial aspect in mitigating the COVID-19 pandemic.
• Hydroxychloroquine and chloroquine are lysosomotropic drugs that affect antigen-presenting pathways and B-cell activation.
• Chloroquine inhibits antibody responses to vaccines, but reports about this effect apparently have not been called to the attention of investigators in the field of COVID-19.
• Studies on immunity to Sars-CoV-2 must take into account treatment regimens for COVID-19.
Introduction
Recent large observational studies indicate that hydroxychloroquine (HY) does not affect outcomes of patients hospitalized with COVID-19 (1, 2) and may even be harmful (3). Results of double-blind, randomized studies to assess efficacy of HY more rigorously are still not available. In spite of these facts, officials are currently advocating use of hydroxychloroquine (HY) for treatment and even prevention of COVID-19. In view of this situation and of the importance of correct interpretation of antibody profiles for planning preventive measures for COVID-19, we would like to bring the attention of readers to studies that raise concerns about the possible impact of HY upon antibody responses to SARS-CoV-2.
Impact of Chloroquine and Derivatives on Responses to Vaccines and Antigen Presentation
In 1986, Pappaionaou et al. (4) recalled the tragic story of a Peace Corps worker in Kenya who succumbed to rabies after being bitten by her rabies-infected pet dog despite having received a full regimen of human diploid-cells rabies vaccine 6 months prior to the bite. The subject had been vaccinated while receiving chloroquine as prophylaxis for malaria. Prompted by this finding, Pappaionaou et al. carried out a randomized controlled trial that showed that chloroquine suppressed antibody responses to the rabies vaccine (4). Subsequently, Fryauff et al. demonstrated a similar effect of chloroquine, but not of primaquine, on antibody responses to tetanus and diphtheria vaccines (5). More recently, Endy et al. showed that antibody responses of individuals vaccinated with a purified chick embryo cell rabies vaccine, given on a postexposure prophylaxis schedule, were significantly lower in individuals receiving chloroquine compared with controls (6).
HY and chloroquine are lysosomotropic drugs that increase the pH of the lysosome, thus affecting functions of proteins involved in antigen presenting pathways and in B-cell activation (7). To the best of our knowledge, there are no new facts in the scientific and medical literature that indicate that the same mechanism could not operate in HY-treated patients suffering from COVID-19 and negatively impact their SARS-CoV-2-specific antibody responses. Indeed, recent findings indicate that some individuals, including hospitalized patients, who have recovered from COVID-19 have not made vigorous IgG antibody responses. However, the most comprehensive publications addressing antibody responses, wherein study subjects presented viability in levels of IgG antibody responses, have not detailed the treatment regimens delivered to the subjects (8–11).
Discussion
Plans for employing immunity profiles against SARS-CoV-2 to relax social distancing and other epidemic mitigation measures and to create “immunity passports” to control spread of COVID-19 have recently been questioned by the World Health Organization because of uncertainty regarding antibody responses (12). As more needs to be learned about the role of antibodies in recovery from and protection against infection with SARS-CoV-2, the impact of HY and other treatment regimens on antibody responses requires systematic evaluation.
Author Contributions
All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.
Funding
This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) (Grant Number 2020/09093-5 to IM).
Conflict of Interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
https://www.frontiersin.org/articles/10.3389/fimmu.2020.01739/full
美国大学2015开始的试验，抗疟疾药物对狂犬病疫苗的影响，认为与其他两种药物相比，氯喹有明显抑制抗体的作用。
Effect of Antimalarial Drugs to Rabies Vaccine for Post-exposure Prophylaxis. (MALRAB)https://clinicaltrials.gov/ct2/show/results/NCT02564471
2020 Mar 2;221(6):927-933. doi: 10.1093/infdis/jiz558. Effect of Antimalarial Drugs on the Immune Response to Intramuscular Rabies Vaccination Using a Postexposure Prophylaxis Regimen Timothy P Endy 1 2, Paul B Keiser 3, Don Cibula 4, Mark Abbott 1, Lisa Ware 1, Stephen J Thomas 1, Mark E Polhemus 1 Affiliations expand PMID: 31743394 DOI: 10.1093/infdis/jiz558 AbstractBackground: Chloroquine can impair the immune responses to intradermal rabies vaccination. Current guidelines recommend an extra intramuscular dose be given for postexposure prophylaxis in previously unvaccinated persons taking any antimalarial drug.
Methods: We conducted a randomized, open-label, single-site study in 103 previously unvaccinated healthy adults age ≥18 to ≤60 years old to evaluate the effects of chloroquine, atovaquone/proguanil (Malarone), and doxycycline on the antibody response to a purified chick embryo cell vaccine, given on a postexposure prophylaxis schedule. All treatment groups received antimalarials 14 days prior to and during vaccination.
Results: All subjects achieved accepted neutralizing antibody titers of ≥0.5 IU/mL following the second rabies vaccination dose and maintained this protection through the duration of the study. We observed a reduction in rabies antibody geometric mean titer in the chloroquine versus control groups 28 days after vaccination: 2.3 versus 6.87 IU/mL, respectively (P < .001, t test). A significant difference was not observed for those taking Malarone or doxycycline.
Conclusions: We conclude that there is no reduction of rabies antibody response in subjects taking Malarone or doxycycline, but a significant reduction in those taking chloroquine; however, accepted antibody levels were achieved for all 3 antimalarials.
Clinical trials registration: NCT02564471.
Keywords: antimalarial drugs; prophylaxis; rabies; vaccination.
https://pubmed.ncbi.nlm.nih.gov/31743394/